2021/10/21 更新

写真a

ミヤザキ イクコ
宮﨑 育子
MIYAZAKI Ikuko
所属
医歯薬学域 講師
職名
講師
外部リンク

学位

  • 博士(医学) ( 岡山大学 )

研究キーワード

  • 神経変性疾患

  • アストロサイト

  • パーキンソン病

  • 神経化学・神経薬理学

研究分野

  • ライフサイエンス / 神経内科学

  • ライフサイエンス / 神経科学一般

学歴

  • 岡山大学   薬学部   製薬化学科

    1993年 - 1997年

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    国名: 日本国

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経歴

  • 岡山大学大学院医歯薬学総合研究科 講師

    2020年9月 - 現在

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  • 岡山大学大学院医歯薬学総合研究科 助教

    2007年 - 2020年8月

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  • 岡山大学大学院医歯薬学総合研究科 助手

    2001年 - 2007年

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  • 岡山大学医学部分子細胞医学研究施設 助手   Medical School

    2000年 - 2001年

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所属学協会

▼全件表示

委員歴

  • 日本パーキンソン病・運動障害疾患学会(MDSJ)   評議員  

    2020年7月 - 現在   

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  • 日本神経精神薬理学会   広報委員  

    2016年11月 - 現在   

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    団体区分:学協会

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  • 日本神経精神薬理学会   評議員  

    2015年 - 現在   

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    団体区分:学協会

    日本神経精神薬理学会

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  • 日本薬理学会   評議員  

    2007年 - 現在   

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    団体区分:学協会

    日本薬理学会

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論文

  • Dopaminergic neuroprotective effects of rotigotine via 5-HT1A receptors: Possibly involvement of metallothionein expression in astrocytes. 査読 国際誌

    Isooka N, Miyazaki I, Kikuoka R, Wada K, Nakayama E, Shin K, Yamamoto D, Kitamura Y, Asanuma M

    Neurochemistry international   132   104608 - 104608   2020年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.neuint.2019.104608

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  • Neuron-astrocyte interactions in Parkinson’s disease. 査読

    Miyazaki I, Asanuma M

    Cells   9   2623   2020年

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    担当区分:筆頭著者, 責任著者   掲載種別:研究論文(学術雑誌)  

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  • Chronic systemic exposure to low-dose rotenone induced central and peripheral neuropathology and motor deficits in mice: Reproducible animal model of Parkinson's disease. 査読

    Miyazaki, I, Isooka, N, Imafuku, F, Sun, J, Kikuoka, R, Furukawa, C, Asanuma, M

    Int. J. Mol. Sci.   21 ( 9 )   3254   2020年

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    担当区分:筆頭著者, 責任著者  

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  • Effects of maternal bisphenol A diglycidyl ether exposure during gestation and lactation on behavior and brain development of the offspring. 査読

    Miyazaki, I, Kikuoka, R, Isooka, N, Takeshima, M, Sonobe, K, Arai, R, Funakoshi, H, Quin, K, Smart, J, Zensho, K, Asanuma, M

    Food and Chemical Toxicol.   138   111235   2020年

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    担当区分:筆頭著者, 責任著者   掲載種別:研究論文(学術雑誌)  

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  • Mirtazapine exerts astrocyte-mediated dopaminergic neuroprotection. 査読

    Kikuoka, R, Miyazaki, I, Kubota, N, Maeda, M, Kagawa, D, Moriyama, M, Sato, A, Murakami, S, Kitamura, Y, Sendo, T, Asanuma, M

    Sci. Rep.   10   20698   2020年

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  • The rotenone models reproducing central and peripheral features of Parkinson's disease. 査読

    Miyazaki I, Asanuma M

    NeuroSci   1 ( 1 )   1 - 14   2020年

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    担当区分:筆頭著者, 責任著者   掲載種別:研究論文(学術雑誌)  

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  • Effects of Enteric Environmental Modification by Coffee Components on Neurodegeneration in Rotenone-Treated Mice. 査読 国際誌

    Miyazaki I, Isooka N, Wada K, Kikuoka R, Kitamura Y, Asanuma M

    Cells   8 ( 3 )   2019年3月

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    担当区分:筆頭著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.3390/cells8030221

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  • Region-Specific Neuroprotective Features of Astrocytes against Oxidative Stress Induced by 6-Hydroxydopamine. 査読 国際誌

    Asanuma M, Okumura-Torigoe N, Miyazaki I, Murakami S, Kitamura Y, Sendo T

    International journal of molecular sciences   20 ( 3 )   2019年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.3390/ijms20030598

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    その他リンク: http://orcid.org/0000-0002-3652-3722

  • Therapeutic strategy of targeting astrocytes for neuroprotection in parkinson’s disease 招待 査読

    Miyazaki I, Asanuma M

    Current Pharmaceutical Design   23 ( 33 )   4936 - 4947   2017年

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    担当区分:筆頭著者, 責任著者   記述言語:英語   出版者・発行元:Bentham Science Publishers B.V.  

    Parkinson’s disease (PD) is one of common neurodegenerative diseases, which shows motor symptoms including tremor, bradykinesia, rigidity and postural instability. It also involves non-motor symptoms such as cognitive impairment, mental manifestation, autonomic disorder and sensory disturbance. Although treatments to improve the motor disability in PD are being assessed at present, the main challenge remains that is the development of neuroprotective or disease-modifying treatments. Therefore, it is desirable to find approaches that can inhibit the progression of dopaminergic neurodegeneration. Astrocytes are known to play an important role in the maintenance of the neuronal environment and exert neuroprotective effects. Additionally, astrocyte dysfunction increases the susceptibility of neurons to cytotoxicity. We have demonstrated neuroprotective approaches in parkinsonian models in various studies targeting astrocytes. In this article, we summarize the neuroprotective function of astrocytes in the brain, involvement of astrocyte dysfunction in neurodegeneration, and experimental approaches to dopaminergic neuroprotection. We review findings reported in several papers including our own studies. We also address target molecules and pivotal pathways in astrocytes for dopaminergic neuroprotection. The review discusses new promising therapeutic strategies to prevent dopaminergic neurodegeneration in PD.

    DOI: 10.2174/1381612823666170710163731

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  • Editorial: Astrocyte-targeted therapeutic strategies for neurological disorders.

    Miyazaki I

    Curr. Pharm. Des.   23 ( 33 )   4933 - 4935   2017年

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    担当区分:筆頭著者, 責任著者  

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  • Neuroprotective effects of levetiracetam target xCT in astrocytes in parkinsonian mice 査読

    Ikuko Miyazaki, Shinki Murakami, Nao Torigoe, Yoshihisa Kitamura, Masato Asanuma

    JOURNAL OF NEUROCHEMISTRY   136 ( 1 )   194 - 204   2016年1月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Astrocytes but not neurons express cystine/glutamate exchange transporter (xCT), which takes up cystine, and consequently supplies the substrate for GSH synthesis in neurons. It is recognized that GSH synthesis in neurons is dependent on the expression of xCT in astrocytes. Previous studies reported that levetiracetam (LEV), an anti-epileptic drug, increased xCT expression invivo. The purpose of this study was to examine neuroprotective effects of LEV in parkinsonian models and demonstrate xCT in astrocytes as a target of neuroprotection against dopaminergic neurodegeneration. We identified striatal astrocytes cultured with LEV showed significant increase in xCT expression and GSH levels. Preincubation of primary cultured mesencephalic dopamine neurons with conditioned media from LEV-treated astrocytes protected against 6-hydroxydopamine (6-OHDA)-induced neurotoxicity. These protective effects were canceled by xCT inhibitor. Furthermore, reduction of nigrostriatal dopaminergic neurons in 6-OHDA-lesioned parkinsonian mice was significantly abrogated by repeated injections of LEV. Treatment with LEV significantly increased the expression of xCT in striatal astrocytes in the hemi-parkinsonian mice. In conclusion, LEV exerts neuroprotective effects against neurodegeneration via up-regulation of xCT and GSH in astrocytes. Thus, xCT in astrocytes could be a potential target in novel neuroprotective approaches to prevent degeneration of dopaminergic neurons.

    DOI: 10.1111/jnc.13405

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  • Serotonin 1A Receptors on Astrocytes as a Potential Target for the Treatment of Parkinson's Disease 査読

    Ikuko Miyazaki, Masato Asanuma

    CURRENT MEDICINAL CHEMISTRY   23 ( 7 )   686 - 700   2016年

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    担当区分:筆頭著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BENTHAM SCIENCE PUBL LTD  

    Astrocytes are the most abundant neuron-supporting glial cells in the central nervous system. The neuroprotective role of astrocytes has been demonstrated in various neurological disorders such as amyotrophic lateral sclerosis, spinal cord injury, stroke and Parkinson's disease (PD). Astrocyte dysfunction or loss-of-astrocytes increases the susceptibility of neurons to cell death, while astrocyte transplantation in animal studies has therapeutic advantage. We reported recently that stimulation of serotonin 1A (5-HT1A) receptors on astrocytes promoted astrocyte proliferation and upregulated antioxidative molecules to act as a neuroprotectant in parkinsonian mice. PD is a progressive neurodegenerative disease with motor symptoms such as tremor, bradykinesia, rigidity and postural instability, that are based on selective loss of nigrostriatal dopaminergic neurons, and with non-motor symptoms such as orthostatic hypotension and constipation based on peripheral neurodegeneration. Although dopaminergic therapy for managing the motor disability associated with PD is being assessed at present, the main challenge remains the development of neuroprotective or disease-modifying treatments. Therefore, it is desirable to find treatments that can reduce the progression of dopaminergic cell death. In this article, we summarize first the neuroprotective properties of astrocytes targeting certain molecules related to PD. Next, we review neuroprotective effects induced by stimulation of 5-HT1A receptors on astrocytes. The review discusses new promising therapeutic strategies based on neuroprotection against oxidative stress and prevention of dopaminergic neurodegeneration.

    DOI: 10.2174/0929867323666160122115057

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  • Serotonin-1A agonist 8-OH-DPAT alleviates motor dysfunction and motor neuron degeneration in a model of amyotrophic lateral sclerosis. 査読

    Miyazaki I, Murakami S, Nakano T, Torigoe N, Kikuoka R, Kitamura Y, Sendo T, Asanuma M

    Ann. Pharmacol. Pharmaceut.   1 ( 1 )   1003 - 1003   2016年

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    担当区分:筆頭著者, 責任著者  

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  • Targeting 5-HT1A receptors in astrocytes to protect dopaminergic neurons in parkinsonian models 査読

    Ikuko Miyazaki, Masato Asanuma, Shinki Murakami, Mika Takeshima, Nao Torigoe, Yoshihisa Kitamura, Ko Miyoshi

    Neurobiology of Disease   59 ( 59 )   244 - 256   2013年11月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Astrocytes are abundant neuron-supporting glial cells that harbor a powerful arsenal of neuroprotective antioxidative molecules and neurotrophic factors. Here we examined whether enrichment with healthy striatal astrocytes can provide neuroprotection against progressive dopaminergic neurodegeneration. Serotonin 1A (5-HT1A) agonist 8-OH-DPAT induced astrocyte proliferation and increased metallothionein-1/-2 (MT-1/-2), antioxidative molecules, in cultured astrocytes and the striatum of mice. Primary cultured mesencephalic dopamine neurons were protected against oxidative stress by preincubation with conditioned media from 8-OH-DPAT-treated astrocytes. These protective effects were canceled by 5-HT1A antagonist or MT-1/-2-specific antibody. Furthermore, reduction of nigrostriatal dopaminergic neurons in 6-hydroxydopamine-lesioned parkinsonian model mice was significantly abrogated by repeated injections of 8-OH-DPAT. Treatment with 8-OH-DPAT markedly increased the expression of MT in striatal astrocytes in the hemi-parkinsonian mice. Our study provides a promising therapeutic strategy of neuroprotection against oxidative stress and progressive dopaminergic neurodegeneration by demonstrating the efficacy of targeting 5-HT1A receptors in astrocytes. © 2013 Elsevier Inc.

    DOI: 10.1016/j.nbd.2013.08.003

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  • Astrocyte-Derived Metallothionein Protects Dopaminergic Neurons from Dopamine Quinone Toxicity 査読

    Ikuko Miyazaki, Masato Asanuma, Yuri Kikkawa, Mika Takeshima, Shinki Murakami, Ko Miyoshi, Norio Sogawa, Taizo Kita

    GLIA   59 ( 3 )   435 - 451   2011年3月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-LISS  

    Our previous studies demonstrated the involvement of quinone formation in dopaminergic neuron dysfunction in the L-DOPA-treated parkinsonian model and in methamphetamine (METH) neurotoxicity. We further reported that the cysteine-rich metal-binding metallothionein (MT) family of proteins protects dopaminergic neurons against dopamine (DA) quinone neurotoxicity by its quinone-quenching property. The aim of this study was to examine MT induction in astrocytes in response to excess DA and the potential neuroprotective effects of astrocyte-derived MTs against DA quinone toxicity. DA exposure significantly upregulated MT-1/-2 in cultured striatal astrocytes, but not in mesencephalic neurons. This DA-induced MT upregulation in astrocytes was blocked by treatment with a DA-transporter (DAT) inhibitor, but not by DA-receptor antagonists. Expression of nuclear factor erythroid 2-related factor (Nrf2) and its binding activity to antioxidant response element of MT-1 gene were significantly increased in the astrocytes after DA exposure. Nuclear translocation of Nrf2 was suppressed by the DAT inhibitor. Quinone formation and reduction of mesencephalic DA neurons after DA exposure were ameliorated by preincubation with conditioned media from DA-treated astrocytes. These protective effects were abrogated by MT-1/-2-specific antibody. Adding exogenous MT-1 to glial conditioned media also showed similar neuroprotective effects. Furthermore, MT-1/-2 expression was markedly elevated specifically in reactive astrocytes in the striatum of L-DOPA-treated hemi-parkinsonian mice or METH-injected mice. These results suggested that excess DA taken up by astrocytes via DAT upregulates MT-1/-2 expression specifically in astrocytes, and that MTs or related molecules secreted specifically by astrocytes protect dopaminergic neurons from damage through quinone quenching and/or scavenging of free radicals. (C)2010 Wiley-Liss, Inc.

    DOI: 10.1002/glia.21112

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  • Neuroprotective Effects of Zonisamide Target Astrocyte 査読

    Masato Asanuma, Ikuko Miyazaki, Francisco J. Diaz-Corrales, Naotaka Kimoto, Yuri Kikkawa, Mika Takeshima, Ko Miyoshi, Miho Murata

    ANNALS OF NEUROLOGY   67 ( 2 )   239 - 249   2010年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-LISS  

    Objective: Recent double-blind, controlled trials in Japan showed that the antiepileptic agent zonisamide (ZNS)improves the cardinal symptoms of Parkinson's disease. Glutathione (GSH) exerts antioxidative activity through quenching reactive oxygen species and dopamine quinone. GSH depletion within dopaminergic neurons impairs mitochondrial complex I activity, followed by age-dependent nigrostriatal neurodegeneration. This study examined changes in GSH and GSH synthesis-related molecules, and the neuroprotective effects of ZNS on dopaminergic neurodegeneration using 6-hydroxydopamine-injected hemiparkinsonian mice brain and cultured neurons or astrocytes.
    Methods and Results: ZNS increased both the cell number and GSH levels in astroglial C6 cells, but not in dopaminergic neuronal CATH.a cells. Repeated injections of ZNS (30mg/kg intraperitoneally) for 14 days also significantly increased GSH levels and S100 beta-positive astrocytes in mouse basal ganglia. Repeated ZNS injections (30mg/kg) for 7 days in the hemiparkinsonian mice increased the expression of cystine/glutamate exchange transporter xCT in activated astrocytes, which supply cysteine to neurons for GSH synthesis. Treatment of these mice with ZNS also increased GSH levels and completely suppressed striatal levodopa-induced quinone formation. Reduction of nigrostriatal dopamine neurons in the lesioned side of hemiparkinsonian mice was significantly abrogated by repeated injections of ZNS with or without adjunctive levodopa starting 3 weeks after 6-hydroxydopamine lesioning.
    Interpretation: These results provide new pharmacological evidence for the effects of ZNS. ZNS markedly increased GSH levels by enhancing the astroglial cystine transport system and/or astroglial proliferation via S100 beta production or secretion. ZNS acts as a neuroprotectant against oxidative stress and progressive dopaminergic neurodegeneration. ANN NEUROL 2010;67:239-249

    DOI: 10.1002/ana.21885

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  • Approaches to Prevent Dopamine Quinone-Induced Neurotoxicity 査読

    Ikuko Miyazaki, Masato Asanuma

    NEUROCHEMICAL RESEARCH   34 ( 4 )   698 - 706   2009年4月

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    担当区分:筆頭著者, 責任著者   記述言語:英語   出版者・発行元:SPRINGER/PLENUM PUBLISHERS  

    Dopamine (DA) and its metabolites containing two hydroxyl residues exert cytotoxicity in dopaminergic neuronal cells, primarily due to the generation of highly reactive DA and DOPA quinones. Quinone formation is closely linked to other representative hypotheses such as mitochondrial dysfunction, inflammation, oxidative stress, and dysfunction of the ubiquitin-proteasome system, in the pathogenesis of neurodegenerative diseases such as Parkinson's disease and methamphetamine-induced neurotoxicity. Therefore, pathogenic effects of the DA quinone have focused on dopaminergic neuron-specific oxidative stress. Recently, various studies have demonstrated that some intrinsic molecules and several drugs exert protective effects against DA quinone-induced damage of dopaminergic neurons. In this article, we review recent studies on some neuroprotective approaches against DA quinone-induced dysfunction and/or degeneration of dopaminergic neurons.

    DOI: 10.1007/s11064-008-9843-1

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  • Dopaminergic neuron-specific oxidative stress caused by dopamine itself

    Ikuko Miyazaki, Masato Asanuma

    ACTA MEDICA OKAYAMA   62 ( 3 )   141 - 150   2008年6月

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    担当区分:筆頭著者, 責任著者   記述言語:英語   出版者・発行元:OKAYAMA UNIV MED SCHOOL  

    Oxidative stress, including the reactive oxygen or nitrogen species generated in the enzymatical oxidation or auto-oxidation of an excess amount of dopamine, is thought to play an important role in dopaminergic neurotoxicity. Dopamine and its metabolites containing 2 hydroxyl residues exert cytotoxicity in dopaminergic neuronal cells, primarily due to the generation of highly reactive dopamine and DOPA quinones. Dopamine and DOPA quinones may irreversibly alter protein function through the formation of 5-cysteinyl-catechols on the proteins. Furthermore, the quinone formation is closely linked to other representative hypotheses such as mitochondrial dysfunction, inflammation, oxidative stress, and dysfunction of the ubiquitin-proteasome system, in the pathogenesis of neurodegenerative diseases. Therefore, pathogenic effects of the dopamine quinone have recently focused on dopaminergic neuron-specific oxidative stress. In this article, we primarily review recent studies on the pathogenicity of quinone formation, in addition to several neuroprotective approaches against dopamine quinone-induced dysfunction of dopaminergic neurons.

    DOI: 10.18926/AMO/30980

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  • Protective effects of metallothionein against dopamine quinone-induced dopaminergic neurotoxicity 査読

    Ikuko Miyazaki, Masato Asanuma, Hiroaki Hozumi, Ko Miyoshi, Norio Sogawa

    FEBS LETTERS   581 ( 25 )   5003 - 5008   2007年10月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE BV  

    Dopamine (DA) quinone as DA neuron-specific oxidative stress conjugates with cysteine residues in functional proteins to form quinoproteins. Here, we examined the effects of cysteine-rich metal-binding proteins, metallothionein (NIT)-1 and -2, on DA quinone-induced neurotoxicity. NIT quenched DA semiquinones in vitro. In dopaminergic cells, DA exposure increased quinoproteins and decreased cell viability; these were ameliorated by pretreatment with MT-inducer zinc. Repeated L-DOPA administration markedly elevated striatal quinoprotein levels and reduced the DA nerve terminals specifically on the lesioned side in NIT-knockout parkinsonian mice, but not in wild-type mice. Our results suggested that intrinsic NIT protects against L-DOPA-induced DA quinone neurotoxicity in parkinsonian mice by its quinone-quenching property. (c) 2007 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.febslet.2007.09.046

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  • Methamphetamine-induced dopaminergic neurotoxicity is regulated by quinone formation-related molecules 査読

    Miyazaki, I, M Asanuma, FJ Diaz-Corrales, M Fukuda, K Kitaichi, K Miyoshi, N Ogawa

    FASEB JOURNAL   20 ( 1 )   571 - +   2006年1月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:FEDERATION AMER SOC EXP BIOL  

    Recently, the neurotoxicity of dopamine (DA) quinone formation by auto-oxidation of DA has focused on dopaminergic neuron-specific oxidative stress. In the present study, we examined DA quinone formation in methamphetamine (METH)-induced dopaminergic neuronal cell death using METH-treated dopaminergic cultured CATH. a cells and METH-injected mouse brain. In CATH. a cells, METH treatment dose-dependently increased the levels of quinoprotein (protein-bound quinone) and the expression of quinone reductase in parallel with neurotoxicity. A similar increase in quinoprotein levels was seen in the striatum of METH (4 mg/kg X4, i.p., 2 h interval)-injected BALB/c mice, coinciding with reduction of DA transporters. Furthermore, pretreatment of CATH. a cells with quinone reductase inducer, butylated hydroxyanisole, significantly and dose-dependently blocked METH-induced elevation of quinoprotein, and ameliorated METH-induced cell death. We also showed the protective effect of tyrosinase, which rapidly oxidizes DA and DA quinone to form stable melanin, against METH-induced dopaminergic neurotoxicity in vitro and in vivo using tyrosinase null mice. Our results indicate that DA quinone formation plays an important role, as a dopaminergic neuron-specific neurotoxic factor, in METH-induced neurotoxicity, which is regulated by quinone formation-related molecules.

    DOI: 10.1096/fj.05-4996fje

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  • Dopamine agonist pergolide prevents levodopa-induced quinoprotein formation in Parkinsonian striatum and shows quenching effects on dopamine-semiquinone generated in vitro 査読

    Ikuko Miyazaki, Masato Asanuma, Francisco J. Diaz-Corrales, Ko Miyoshi, Norio Ogawa

    Clinical Neuropharmacology   28 ( 4 )   155 - 160   2005年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The neurotoxicity of dopamine (DA) quinones that appears in dopaminergic neuron-specific oxidative stress has recently been shown to play a role in the pathogenesis and/or progression of Parkinson disease. To clarify the effects of a DA agonist, pergolide, on the levodopa-induced elevation of quinones, the authors examined, striatal changes in quinoprotein using a hemi-parkinsonian mouse model. The level of striatal quinoprotein was significantly elevated specifically on the parkinsonian side, but not on the control side, after repeated levodopa administration. This levodopa-induced increase in striatal quinoprotein was almost completely suppressed by adjunctive administration with pergolide on the lesioned side. Furthermore, it was clarified that pergolide scavenged DA-semiquinones generated in vitro in a dose-dependent manner. These suppressive and quenching effects of pergolide against cytotoxic DA quinones may play a key role in its neuroprotective mechanism in the parkinsonian brain. Copyright © 2005 by Lippincott Williams &amp
    Wilkins.

    DOI: 10.1097/01.wnf.0000175523.33334.24

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  • Direct evidence for expression of dopamine receptors in astrocytes from basal ganglia 査読

    Miyazaki, I, M Asanuma, FJ Diaz-Corrales, K Miyoshi, N Ogawa

    BRAIN RESEARCH   1029 ( 1 )   120 - 123   2004年12月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE BV  

    Expression of dopamine receptors (DA-Rs) in astrocytes was examined in vitro and in vivo using primary cultured astrocytes and brain slices from rat basal ganglia. Astrocytes from basal ganglia expressed DA D1-, D3-, D4- and D5-receptors and D4-mediated signal transduction in response to DA, suggesting possible involvement of astrocytes in the pharmacological action of atypical antipsychotic drugs and in DA response in some neurological diseases. (C) 2004 Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.brainres.2004.09.014

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  • Age-related changes in expression of metallothionein-III in rat brain 査読

    Miyazaki, I, M Asanuma, Y Higashi, CA Sogawa, K Tanaka, N Ogawa

    NEUROSCIENCE RESEARCH   43 ( 4 )   323 - 333   2002年8月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCI IRELAND LTD  

    Metallothionein (MT)-III is a metal binding protein, called growth inhibitory factor, and is mainly expressed in the central nervous system. Since MT-III decreases in the brain of Alzheimer's disease (AD), a growing interest has been focused on its relationship to neurodegenerative diseases. To clarify age-related changes in the MT-III expression and its inducibility against oxidative stress, we analyzed the expression of MT-III and its mRNA in the brain of lipopolysaccharide (LPS)-treated aged rats. In the frontal cortex, basal expression of MT-III mRNA was significantly increased with aging, while it was observed no induction of MT-III mRNA against LPS administration in the aged rat brain. MT-III immunopositive cells were increased in the frontal, parietal and piriform cortices, hypothalamus and amygdaloid nucleus with aging. The LPS treatment induced MT-III expression in the brain of young-adult rats, but not in the aged rat brain. Furthermore, the MT-III induction with LPS treatment was mainly observed in oligodendrocyte and microglia. In the present study, we showed that inducibility of brain MT-III against oxidative stress may be reduced with aging. Since it has been reported that MT-III has neuroprotective roles as an antioxidant, present results suggest that MT-III is closely related to the neurodegeneration in the aged animals. (C) 2002 Elsevier Science Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

    DOI: 10.1016/S0168-0102(02)00057-3

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  • Expression of metallothionein-III mRNA and its regulation by levodopa in the basal ganglia of hemi-parkinsonian rats 査読

    Miyazaki, I, CA Sogawa, M Asanuma, Y Higashi, K Tanaka, T Nakanishi, N Ogawa

    NEUROSCIENCE LETTERS   293 ( 1 )   65 - 68   2000年10月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCI IRELAND LTD  

    In the brain, metallothionein (MT)-III exhibits a free radical scavenging activity. Here we examined the expression of MT-III mRNA in the basal ganglia of 6-hydroxydopamine (6-OHDA)-lesioned hemi-parkinsonian rats and its regulation by levodopa. The level of MT-III mRNA was significantly decreased in the striatum of 6-OHDA-lesioned side. Levodopa treatment significantly increased the expression of striatal MT-III mRNA in the non-lesioned side, but showed no significant effect in the 6-OHDA-lesioned side. These results suggest that the regulation of MT-III mRNA may be related to the progressive degeneration in parkinsonism. (C) 2000 Published by Elsevier Science Ireland Ltd.

    DOI: 10.1016/S0304-3940(00)01488-9

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  • Bifemelane hydrochloride protects against cytotoxicity of hydrogen peroxide on cultured rat neuroblastoma cell line 査読

    Miyazaki, I, E Iwata-Ichikawa, M Asanuma, M Iida, N Ogawa

    NEUROCHEMICAL RESEARCH   24 ( 7 )   857 - 860   1999年7月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:KLUWER ACADEMIC/PLENUM PUBL  

    Free radicals are involved in neuronal damage. Bifemelane hydrochloride has been reported to protect neural tissues against ischemic damage and age-related neurodegeneration. We examined the protective effects of bifemelane HCl and the relation between its effectiveness and free radical formation in hydrogen peroxide (H2O2)-induced cytotoxicity using cultured rat neuroblastoma cell line (B50). Cytotoxicity was examined by using the lactate dehydrogenase (LDH) assay and cell viability by the WST-1 assay. H2O2 reduced the survival of B50 cells in a dose-dependent manner, and treatment of these cells with 75 mu M or 100 mu M H2O2 reduced their viability by 50% relative to the control group. B50 cells were treated with 5 or 10 mu M bifemelane for 2 days followed by treatment with 75 mu M or 100 mu M H2O2 H2O2 cytotoxicity was reduced by pretreatment with bifemelane. We also examined the effect of bifemelane on lipid peroxide formation in B50 cells using thiobarbituric acid reactive substances assay. Pretreatment of B50 cells with 10 mu M bifemelane for 2 days reduced lipid peroxide formation to approximately 54% of the control group. Our results suggest that bifemelane hydrochloride provides a protective effect against H2O2 cytotoxicity partly due to its anti-oxidative properties.

    DOI: 10.1023/A:1020953913490

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  • Cerebellar Blood Flow and Gene Expression in Crossed Cerebellar Diaschisis after Transient Middle Cerebral Artery Occlusion in Rats. 査読 国際誌

    Kidani, N, Hishikawa, T, Hiramatsu, M, Nishihiro, S, Kin, K, Takahashi, Y, Murai, S, Sugiu, K, Yasuhara, T, Miyazaki, I, Asanuma, M, Date, I

    International journal of molecular sciences   21 ( 11 )   2020年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Crossed cerebellar diaschisis (CCD) is a state of hypoperfusion and hypometabolism in the contralesional cerebellar hemisphere caused by a supratentorial lesion, but its pathophysiology is not fully understood. We evaluated chronological changes in cerebellar blood flow (CbBF) and gene expressions in the cerebellum using a rat model of transient middle cerebral artery occlusion (MCAO). CbBF was analyzed at two and seven days after MCAO using single photon emission computed tomography (SPECT). DNA microarray analysis and western blotting of the cerebellar cortex were performed and apoptotic cells in the cerebellar cortex were stained. CbBF in the contralesional hemisphere was significantly decreased and this lateral imbalance recovered over one week. Gene set enrichment analysis revealed that a gene set for "oxidative phosphorylation" was significantly upregulated while fourteen other gene sets including "apoptosis", "hypoxia" and "reactive oxygen species" showed a tendency toward upregulation in the contralesional cerebellum. MCAO upregulated the expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in the contralesional cerebellar cortex. The number of apoptotic cells increased in the molecular layer of the contralesional cerebellum. Focal cerebral ischemia in our rat MCAO model caused CCD along with enhanced expression of genes related to oxidative stress and apoptosis.

    DOI: 10.3390/ijms21114137

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  • The neurotoxicity of psychoactive phenethylamines "2C series" in cultured monoaminergic neuronal cell lines. 査読

    Asanuma, M, Miyazaki, I, Funada, M

    Forensic Toxicol.   2020年

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    掲載種別:研究論文(学術雑誌)  

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  • N-acetylcysteine attenuates the anxiety-like behavior and spatial cognition impairment induced by doxorubicin and cyclophosphamide combination treatment in rats. 査読

    Kitamura, Y, Ushio S, Sumiyoshi, Y, Wada, Y, Miyazaki, I, Asanuma, M, Sendo, T

    Pharmacology   2020年

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  • Attenuation of Macrophage Migration Inhibitory Factor-Stimulated Signaling via S-Nitrosylation. 査読

    Nakahara K, Fujikawa K, Hiraoka H, Miyazaki I, Asanuma M, Ito A, Takasugi N, Uehara T

    Biological & pharmaceutical bulletin   42 ( 6 )   1044 - 1047   2019年

  • Involvement of 5-HT<sub>2A</sub> receptor hyperfunction in the anxiety-like behavior induced by doxorubicin and cyclophosphamide combination treatment in rats. 査読

    Nakamura Y, Kitamura Y, Sumiyoshi Y, Naito N, Kan S, Ushio S, Miyazaki I, Asanuma M, Sendo T

    Journal of pharmacological sciences   138 ( 3 )   192 - 197   2018年10月

  • Neuroprotective effect of fermented papaya preparation by activation of Nrf2 pathway in astrocytes 査読

    Murakami S, Miyazaki I, Asanuma M

    Nutritional Neuroscience   21 ( 3 )   176 - 184   2018年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Taylor and Francis Ltd.  

    Objectives: Nuclear factor erythroid 2-related factor (Nrf2) in astrocyte plays important roles in brain homeostasis. Fermented papaya preparation (FPP) has anti-oxidative, anti-inflammatory, immunoregulatory properties. The present study investigated the effects of FPP on activation of Nrf2 and release of Nrf2-regulated neuroprotective antioxidants and detoxifying molecules. Methods: Primary cultured astrocytes from rat embryos were treated with FPP for 6 or 24 hours. The expression levels of nuclear Nrf2 and cytoplasmic Nrf2-regulated molecules were determined by western blot analysis and immunohistochemistry. Glutathione levels were measured in cells and medium. Dopaminergic neurons were exposed 6-hydroxydopamine (6-OHDA) with/without pre-treatment with FPP astrocytes. Mice were treated orally with FPP for 2 weeks. Results: FPP increased nuclear translocation of Nrf2 in striatal astrocytes, induced up-regulation of NAD(P)H quinine oxidoreductase-1, glutathione-S transferase and hemeoxygenase-1, and increased glutathione level and the percentage of metallothionein-expressing astrocytes. Moreover, FPP suppressed 6-OHDA-induced dopaminergic neuronal loss in not only neuron-astrocyte mixed culture, but also neuron-rich cultures pre-treated with glial conditioned medium. Two-week oral treatment of mice with FPP resulted in Nrf2 activation and increase in glutathione level in striatum. Discussion: The results indicated that FPP enhances the anti-oxidative capacity through activation of Nrf2 in astrocytes, suggesting it may provide neuroprotection in oxidative stress-related neurodegenerative diseases.

    DOI: 10.1080/1028415X.2016.1253171

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  • Influence of nicotine on doxorubicin and cyclophosphamide combination treatment-induced spatial cognitive impairment and anxiety-like behavior in rats 査読

    Kitamura Y, Kanemoto E, Sugimoto M, Machida A, Nakamura Y, Naito N, Kanzaki H, Miyazaki I, Asanuma M, Sendo T

    NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY   390 ( 4 )   369 - 378   2017年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER  

    In the present study, we examined the effects of nicotine on cognitive impairment, anxiety-like behavior, and hippocampal cell proliferation in rats treated with a combination of doxorubicin and cyclophosphamide. Combined treatment with doxorubicin and cyclophosphamide produced cognitive impairment and anxiety-like behavior in rats. Nicotine treatment reversed the inhibition of novel location recognition induced by the combination treatment. This effect of nicotine was blocked by methyllycaconitine, a selective alpha 7 nicotinic acetylcholine receptor (nAChR) antagonist, and dihydro-beta-erythroidine, a selective alpha 4 beta 2 nAChR antagonist. In addition, nicotine normalized the amount of spontaneous alternation seen during the Y-maze task, which had been reduced by the combination treatment. This effect of nicotine was inhibited by dihydro-beta-erythroidine. In comparison, nicotine did not affect the anxiety-like behavior induced by the combination treatment. Furthermore, the combination treatment reduced the number of proliferating cells in the subgranular zone of the hippocampal dentate gyrus, and this was also prevented by nicotine. Finally, the combination of doxorubicin and cyclophosphamide significantly reduced hippocampal alpha 7 nAChR mRNA expression. These results suggest that nicotine inhibits doxorubicin and cyclophosphamide-induced cognitive impairment via alpha 7 nAChR and alpha 4 beta 2 nAChR, and also enhances hippocampal neurogenesis.

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  • L-Theanine protects against excess dopamine-induced neurotoxicity in the presence of astrocytes 査読

    Takeshima M, Miyazaki I, Murakami S, Kita T, Asanuma M

    JOURNAL OF CLINICAL BIOCHEMISTRY AND NUTRITION   59 ( 2 )   93 - 99   2016年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:JOURNAL CLINICAL BIOCHEMISTRY & NUTRITION  

    L-Theanine (gamma-glutamylethylamide), a component of green tea, is considered to have regulatory and neuroprotective roles in the brain. The present study was designed to determine the effect of L-theanine on excess dopamine-induced neurotoxicity in both cell culture and animal experiments. The primary cultured mesencephalic neurons or co-cultures of mesencephalic neurons and striatal astrocytes were pretreated with L-theanine for 72 h, and then treated with excess dopamine for further 24 h. The cell viability of dopamine neurons and levels of glutathione were evaluated. Excess dopamine-induced neurotoxicity was significantly attenuated by 72 h preincubation with L-theanine in neuron-astrocyte co-cultures but not in neuron-rich cultures. Exposure to L-theanine increased the levels of glutathione in both astrocytes and glial conditioned medium. The glial conditioned medium from L-theanine-pretreated striatal astrocytes attenuated dopamine-induced neurotoxicity and quinoprotein formation in mesencephalic neurons. In addition, replacement of L-glutamate with L-theanine in an in vitro cell-free glutathione-synthesis system produced glutathione-like thiol compounds. Furthermore, L-theanine administration (4 mg/kg, p.o.) for 14 days significantly increased glutathione levels in the striatum of mice. The results suggest that L-theanine provides neuroprotection against oxidative stress-induced neuronal damage by humoral molecules released from astrocytes, probably including glutathione.

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  • 3-O-Methyldopa inhibits astrocyte-mediated dopaminergic neuroprotective effects of L-DOPA 査読

    Asanuma M, Miyazaki I

    BMC NEUROSCIENCE   17 ( 1 )   2016年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BIOMED CENTRAL LTD  

    Background: We evaluated the effects of 3-O-methyldopa (3-OMD), a metabolite of L-DOPA which is formed by catechol-O-methyltransferase (COMT), on the uptake, metabolism, and neuroprotective effects of L-DOPA in striatal astrocytes. We examined changes in the numbers of dopaminergic neurons after treatment with L-DOPA and 3-OMD or entacapone, a peripheral COMT inhibitor, using primary cultured mesencephalic neurons and striatal astrocytes.
    Results: The number of tyrosine hydroxylase-positive dopaminergic neurons was not affected by L-DOPA treatment in mesencephalic neurons alone. However, the increase in viability of dopaminergic neurons in the presence of astrocytes was further enhanced after methyl-L-DOPA treatment (25 mu M) in mixed cultured mesencephalic neurons and striatal astrocytes. The neuroprotective effect of 25 mu M L-DOPA was almost completely inhibited by simultaneous treatment with 3-OMD (10 or 100 mu M), and was enhanced by concomitant treatment with entacapone (0.3 mu M). The uptake of L-DOPA into and the release of glutathione from striatal astrocytes after L-DOPA treatment (100 mu M) were inhibited by simultaneous exposure to 3-OMD (100 mu M).
    Conclusions: These data suggest that L-DOPA exerts its neuroprotective effect on dopaminergic neurons via astrocytes and that 3-OMD competes with L-DOPA by acting on target molecule(s) (possibly including glutathione) released from astrocytes. Since some amount of entacapone can cross the blood-brain barrier, this reagent may enhance L-DOPA transportation by inhibiting COMT and increase the astrocyte-mediated neuroprotective effects of L-DOPA on dopaminergic neurons.

    DOI: 10.1186/s12868-016-0289-0

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  • In vitro quantitative determination of the concentration of the polymerization agent methyl 2-benzoylbenzoate in intravenous injection solution and the cytotoxic effects of the chemical on normal human peripheral blood mononuclear cells 査読

    Tsuboi C, Kawasaki Y, Yoshitome K, Yagi K, Miura T, Esumi S, Miyazaki I, Asanuma M, Kitamura Y, Sendo T

    ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH   23 ( 10 )   10262 - 10269   2016年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER HEIDELBERG  

    In previous studies, we detected the photoinitiators 1-hydroxycyclohexyl phenyl ketone (1-HCHPK) and 2-methyl-4'-(methylthio)-2-morpholinopropiophenone (MTMP) in an intravenous injection solution. Importantly, 1-HCHPK and MTMP have been demonstrated to be cytotoxic to normal human peripheral blood (PB) mononuclear cells (MNC). Cell death (apoptosis) pathways can be classified into two modes, caspase-dependent and -independent pathways. However, it is unclear whether methyl 2-benzoylbenzoate (MBB) induces the caspase-dependent and/or -independent pathway in normal human PBMNC. In the present in vitro study, we examined the levels of MBB in a solution from an intravenous fluid bag and the cytotoxicity of MBB towards normal human PBMNC via the caspase-8-, caspase-9-, or apoptosis-inducing factor (AIF)-mediated apoptosis pathways. We found that extracts from the injection solution had been contaminated with approximately 80 mu M of the photoinitiator MBB. In addition, MBB induced apoptosis in the high concentration range in normal human PBMNC in vitro. Moreover, we found that MBB-induced apoptosis occurs via the caspase-9 pathway, but not the AIF pathway. In conclusion, we suggest that MBB has cytotoxic effects on normal human PBMNC in vitro, which are mediated via the caspase-dependent pathway.

    DOI: 10.1007/s11356-016-6332-y

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  • Anti-high mobility group box 1 antibody exerts neuroprotection in a rat model of Parkinson's disease 査読

    Tatsuya Sasaki, Keyue Liu, Takashi Agari, Takao Yasuhara, Jun Morimoto, Mihoko Okazaki, Hayato Takeuchi, Atsuhiko Toyoshima, Susumu Sasada, Aiko Shinko, Akihiko Kondo, Masahiro Kameda, Ikuko Miyazaki, Masato Asanuma, Cesario V. Borlongan, Masahiro Nishibori, Isao Date

    EXPERIMENTAL NEUROLOGY   275 ( 1 )   220 - 231   2016年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    The high mobility group box-1 (HMGB1) exists as an architectural nuclear protein in the normal state, but displays an inflammatory cytokine-like activity in the extracellular space under pathological condition. Inflammation in the pathogenesis of Parkinson's disease (PD) has been documented. In this study, we investigated the involvement of HMGB1 in the pathology and the neuroprotective effects of neutralizing anti-HMGB1 monoclonal antibody (mAb) on an animal model of PD. Adult female Sprague-Dawley rats were initially injected with 6-hydroxydopmaine (6-OHDA, 20 mu g/4 mu l) into the right striatum, then anti-HMGB1 mAb (1 mg/kg), or control mAb was intravenously administered immediately, at 6 and 24 h after 6-OHDA injection. The treatment with anti-HMGB1 mAb significantly preserved dopaminergic neurons in substantia nigra pars compacta and dopaminergic terminals inherent in the striatum, and attenuated PD behavioral symptoms compared to the control mAb-treated group. HMGB1 was retained in the nucleus of neurons and astrocytes by inhibiting the proinflammation-induced oxidative stress in the anti-HMGB1 mAb-treated group, whereas HMGB1 translocation was observed in neurons at 1 day and astrocytes at 7 days after 6-OHDA injection in the control mAb-treated group. Anti-HMGB1 mAb inhibited the activation of microglia, disruption of blood-brain-barrier (BBB), and the expression of inflammation cytokines such as IL-1 beta. and IL-6. These results suggested that HMGB1 released from neurons and astrocytes was at least partly involved in the mechanism and pathway of degeneration of dopaminergic neurons induced by 6-0HDA exposure. Intravenous administration of anti-HMGB1 mAb stands as a novel therapy for PD possibly acting through the suppression of neuroinflammation and the attenuation of disruption of BOB associated with the disease. (C) 2015 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.expneurol.2015.11.003

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  • Changes in Metallothionein Isoform Expression in the Bones of Ovariectomized Rats 査読

    Sogawa C, Ikegame M, Miyazaki I, Ara T, Imamura Y, Okusha Y, Ohyama K, Asanuma M, Sogawa N, Yamamoto T, Kozaki K

    JOURNAL OF HARD TISSUE BIOLOGY   25 ( 1 )   21 - 26   2016年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:JOURNAL HARD TISSUE BIOLOGY  

    Metal-binding proteins, metallothioneins (MTs), may play important roles in bone metabolism. However, the contribution of MTs to bone metabolism remains obscure. In the present study, we investigated the expression of MT isoforms in bone cells and mRNA for MT isoforms in the tibiae following ovariectomy (OVX). The results obtained showed that MT-I/II and MT-III were expressed in osteoblasts, osteoclasts, and osteocytes 4 weeks after OVX. Peaks in the mRNA expression ratios (OVX/Sham) of MT-I/II and MT-III changed following OVX. The expression ratio of MT-I/II increased after 1 week, whereas that of MT-III increased 4 weeks after OVX. These results suggest that the contribution of MTs to bone metabolism may depend on the isoforms in the cell types and the stage after OVX.

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  • Doxorubicin and cyclophosphamide treatment produces anxiety-like behavior and spatial cognition impairment in rats: Possible involvement of hippocampal neurogenesis via brain-derived neurotrophic factor and cyclin D1 regulation 査読

    Yoshihisa Kitamura, Sayo Hattori, Saori Yoneda, Saori Watanabe, Erika Kanemoto, Misaki Sugimoto, Toshiki Kawai, Ayumi Machida, Hirotaka Kanzaki, Ikuko Miyazaki, Masato Asanuma, Toshiaki Sendo

    BEHAVIOURAL BRAIN RESEARCH   292   184 - 193   2015年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE BV  

    Many patients who have received chemotherapy to treat cancer experience depressive- and anxiety-like symptoms or cognitive impairment. However, despite the evidence for this, the underlying mechanisms are still not understood. This study investigated behavioral and biochemical changes upon treatment with doxorubicin and cyclophosphamide, focusing on mental and cognitive systems, as well as neurogenesis in male rats. Doxorubicin (2 mg/kg), cyclophosphamide (50 mg/kg), and the combination of doxorubicin and cyclophosphamide were injected intraperitoneally once per week for 4 weeks. In particular, the co-administration of doxorubicin and cyclophosphamide produced anhedonia-like, anxiety-like, and spatial cognitive impairments in rats. It also reduced both the number of proliferating cells in the subgranular zone of the hippocampal dentate gyrus and their survival. Serum brain-derived neurotrophic factor (BDNF) levels were decreased along with chemotherapy-induced decreases in platelet levels. However, hippocampal BDNF levels and Bdnf mRNA levels were not decreased by this treatment. On the other hand, hippocampal cyclin D1 levels were significantly decreased by chemotherapy. These results suggest that the co-administration of doxorubicin and cyclophosphamide induces psychological and cognitive impairment, in addition to negatively affecting hippocampal neurogenesis, which may be related to hippocampal cyclin D1 levels, but not hippocampal BDNF levels. (C) 2015 Elsevier B.V. All rights reserved.

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  • Long-Term Systemic Exposure to Rotenone Induces Central and Peripheral Pathology of Parkinson's Disease in Mice 査読

    Shinki Murakami, Ikuko Miyazaki, Ko Miyoshi, Masato Asanuma

    NEUROCHEMICAL RESEARCH   40 ( 6 )   1165 - 1178   2015年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER/PLENUM PUBLISHERS  

    Parkinson's disease (PD) is a progressive neurodegenerative disease with motor and non-motor symptoms that precede the onset of motor symptoms. Rotenone is often used to induce PD-like pathology in the central nervous system (CNS) and enteric nervous system (ENS). However, there is little or no information on the temporal changes in other neural tissues and the spread of pathology throughout the entire body organs. Here, we recorded the serial immunohistochemical changes in neurons and glial cells of the striatum, substantia nigra (SN), olfactory bulb (OB), thoracic cord (ThC) and ascending colon (AC) induced by 1-, 3- and 6-week administration of rotenone (50 mg/kg/day) infused subcutaneously in C57BL mice using an osmotic pump. Rotenone exposure for 3 or 6 weeks caused neurodegeneration in the striatum, whereas neuronal damage was seen in the SN and OB only after 6 weeks. Moreover, rotenone induced neurodegeneration in the myenteric plexus of AC but not in ThC. Rotenone also activated glial cells before any apparent neurodegeneration in the CNS but not in the ENS. Our results demonstrated that subcutaneous administration of rotenone can cause progressive neurodegeneration in the OB and AC, in addition to the nigrostriatal pathway, and temporal differential glial activation, and that these changes do not spread retrogradely from OB or ENS to nigrostriatal pathway. The results suggested that the different vulnerability of neurons to the neurotoxic effects of rotenone administrated subcutaneously are due to glial activation in these neural tissues.

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  • ハルミンの薬物依存性ならびに細胞毒性の評価:植物由来幻覚成分の有害作用について.

    舩田正彦, 竹林美佳, 宮崎育子, 浅沼幹人, 青尾直也, 和田 清

    精神保健研究   61 ( 28 )   61 - 72   2015年

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  • Visualization of Astrocytic Primary Cilia in the Mouse Brain by Immunofluorescent Analysis Using the Cilia Marker Arl13b 査読

    Kyosuke Kasaharaa, Ko Miyoshi, Shinki Murakami, Ikuko Miyazaki, Masato Asanuma

    ACTA MEDICA OKAYAMA   68 ( 6 )   317 - 322   2014年12月

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    記述言語:英語   出版者・発行元:OKAYAMA UNIV MED SCHOOL  

    In vertebrates, almost all somatic cells extend a single immotile cilium, referred to as a primary cilium. Increasing evidence suggests that primary cilia serve as cellular antennae in many types of tissues by sensing chemical or mechanical stimuli in the milieu surrounding the cells. In rodents an antibody to adenylyl cyclase 3 (AC3) has been widely used to label the primary cilia of neurons in vivo by immunostaining, whereas the lack of markers for the primary cilia of astrocytes has made it difficult to observe astrocytic primary cilia in vivo. Here, we obtained a visualization of astrocytic primary cilia in the mouse brain. In the somatosensory cortex, a large portion of neurons and astrocytes at postnatal day 10 (P10), and of neurons at P56 had AC3-positive primary cilia, whereas only approx. one-half of the astrocytes in the P56 mice carried primary cilia weakly positive for AC3. In contrast, the majority of astrocytes had ADP-ribosylation factor-like protein 13B (Arl13b)-positive primary cilia in the somatosensory cortex and other brain regions of P56 mice. The lengths of astrocytic primary cilia positive for Arl13b varied among the brain regions. Our data indicate that Arl13b is a noteworthy marker of astrocytic primary cilia in the brain.

    DOI: 10.18926/AMO/53020

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  • Neuroprotective Effects of Metallothionein Against Rotenone-Induced Myenteric Neurodegeneration in Parkinsonian Mice 査読

    Shinki Murakami, Ikuko Miyazaki, Norio Sogawa, Ko Miyoshi, Masato Asanuma

    NEUROTOXICITY RESEARCH   26 ( 3 )   285 - 298   2014年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER  

    Parkinson's disease (PD) is a neurodegenerative disease with motor symptoms as well as non-motor symptoms that precede the onset of motor symptoms. Mitochondrial complex I inhibitor, rotenone, has been widely used to reproduce PD pathology in the central nervous system (CNS) and enteric nervous system (ENS). We reported previously that metallothioneins (MTs) released from astrocytes can protect dopaminergic neurons against oxidative stress. The present study examined the changes in MT expression by chronic systemic rotenone administration in the striatum and colonic myenteric plexus of C57BL mice. In addition, we investigated the effects of MT depletion on rotenone-induced neurodegeneration in CNS and ENS using MT-1 and MT-2 knockout (MT KO) mice, or using primary cultured neurons from MT KO mice. In normal C57BL mice, subcutaneous administration of rotenone for 6 weeks caused neurodegeneration, increased MT expression with astrocytes activation in the striatum and myenteric plexus. MT KO mice showed more severe myenteric neuronal damage by rotenone administration after 4 weeks than wild-type mice, accompanied by reduced astroglial activation. In primary cultured mesencephalic neurons from MT KO mice, rotenone exposure induced neurotoxicity in dopaminergic neurons, which was complemented by addition of recombinant protein. The present results suggest that MT seems to provide protection against neurodegeneration in ENS of rotenone-induced PD model mice.

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  • Methylphenidate improves learning impairments and hyperthermia-induced seizures caused by an Scn1a mutation 査読

    Iori Ohmori, Nozomi Kawakami, Sumei Liu, Haijiao Wang, Ikuko Miyazaki, Masato Asanuma, Hiroyuki Michiue, Hideki Matsui, Tomoji Mashimo, Mamoru Ouchida

    EPILEPSIA   55 ( 10 )   1558 - 1567   2014年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    ObjectiveDevelopmental disorders including cognitive deficit, hyperkinetic disorder, and autistic behaviors are frequently comorbid in epileptic patients with SCN1A mutations. However, the mechanisms underlying these developmental disorders are poorly understood and treatments are currently unavailable. Using a rodent model with an Scn1a mutation, we aimed to elucidate the pathophysiologic basis and potential therapeutic treatments for developmental disorders stemming from Scn1a mutations.MethodsWe conducted behavioral analyses on rats with the N1417H-Scn1a mutation. With high-performance liquid chromatography, we measured dopamine and its metabolites in the frontal cortex, striatum, nucleus accumbens, and midbrain. Methylphenidate was administered intraperitoneally to examine its effects on developmental disorder-like behaviors and hyperthermia-induced seizures.ResultsBehavioral studies revealed that Scn1a-mutant rats had repetitive behavior, hyperactivity, anxiety-like behavior, spatial learning impairments, and motor imbalance. Dopamine levels in the striatum and nucleus accumbens in Scn1a-mutant rats were significantly lower than those in wild-type rats. In Scn1a-mutant rats, methylphenidate, by increasing dopamine levels in the synaptic cleft, improved hyperactivity, anxiety-like behavior, and spatial learning impairments. Surprisingly, methylphenidate also strongly suppressed hyperthermia-induced seizures.SignificanceDysfunction of the mesolimbic dopamine reward pathway may contribute to the hyperactivity and learning impairments in Scn1a-mutant rats. Methylphenidate was effective for treating hyperactivity, learning impairments, and hyperthermia-induced seizures. We propose that methylphenidate treatment may ameliorate not only developmental disorders but also epileptic seizures in patients with SCN1A mutations.

    DOI: 10.1111/epi.12750

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  • Striatal Astrocytes Act as a Reservoir for L-DOPA 査読

    Masato Asanuma, Ikuko Miyazaki, Shinki Murakami, Francisco J. Diaz-Corrales, Norio Ogawa

    PLOS ONE   9 ( 9 )   e106362   2014年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PUBLIC LIBRARY SCIENCE  

    L-DOPA is therapeutically efficacious in patients with Parkinson's disease (PD), although dopamine (DA) neurons are severely degenerated. Since cortical astrocytes express neutral amino acid transporter (LAT) and DA transporter (DAT), the uptake and metabolism of L-DOPA and DA in striatal astrocytes may influence their availability in the dopaminergic system of PD. To assess possible L-DOPA-and DA-uptake and metabolic properties of striatal astrocytes, we examined the expression of L-DOPA, DA and DAT in striatal astrocytes of hemi-parkinsonian model rats after repeated L-DOPA administration, and measured the contents of L-DOPA, DA and their metabolite in primary cultured striatal astrocytes after L-DOPA/DA treatment. Repeated injections of L-DOPA induced apparent L-DOPA-and DA-immunoreactivities and marked expression of DAT in reactive astrocytes on the lesioned side of the striatum in hemi-parkinsonian rats. Exposure to DA for 4 h significantly increased the levels of DA and its metabolite DOPAC in cultured striatal astrocytes. L-DOPA was also markedly increased in cultured striatal astrocytes after 4-h L-DOPA exposure, but DA was not detected 4 or 8 h after L-DOPA treatment, despite the expression of aromatic amino acid decarboxylase in astrocytes. Furthermore, the intracellular level of L-DOPA in cultured striatal astrocytes decreased rapidly after removal of extracellular L-DOPA. The results suggest that DA uptaken into striatal astrocytes is rapidly metabolized and that striatal astrocytes act as a reservoir of L-DOPA that govern the uptake or release of L-DOPA depending on extracellular L-DOPA concentration, but are less capable of converting L-DOPA to DA.

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  • Effects of (+)-8-OH-DPAT on the duration of immobility during the forced swim test and hippocampal cell proliferation in ACTH-treated rats 査読

    Ayaka Miyake, Yoshihisa Kitamura, Ikuko Miyazaki, Masato Asanuma, Toshiaki Sendo

    PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR   122   240 - 245   2014年7月

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    記述言語:英語   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    In the present study, we examined the effect of ACTH on the immobilization of rats in the forced swim test and hippocampal cell proliferation after administration of the 5-HT1A receptor agonist, R-(+)-8-hydroxy-2-di-n-propylamino tetralin ((+)-8-OH-DPAT). Chronic treatment with (+)-8-OH-DPAT (0.01-0.1 mg/kg, s.c.) significantly decreased the duration of immobility in saline- and ACTH-treated rats. Chronic administration of ACTH caused a significant decrease in hippocampal cell proliferation. However, (+)-8-OH-DPAT significantly normalized cell proliferation in ACTH-treated rats. We then investigated the effects of (+)-8-OH-DPAT on the expression of brain-derived neurotrophic factor (BDNF) and cyclin D1 (elements of cyclic adenosine monophosphate response element-binding protein (CREB)-BDNF and Wnt signaling pathways, respectively) in the hippocampus of saline- and ACTH-treated rats. ACTH treatment significantly decreased the expression of cyclin D1, while treatment with (+)-8-OH-DPAT normalized the expression of cyclin D1 in ACTH-treated rats. However, the expression of BDNF did not change in either saline- or ACTH-treated rats. These findings suggest that the antidepressant effects of (+)-8-OH-DPAT in treatment-resistant animals may be attributed to an enhancement of hippocampal cell proliferation, at least in part due to an enhancement of cyclin D1 expression. (C) 2014 Elsevier Inc All rights reserved.

    DOI: 10.1016/j.pbb.2014.04.003

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  • Lack of Dopaminergic Inputs Elongates the Primary Cilia of Striatal Neurons 査読

    Ko Miyoshi, Kyosuke Kasahara, Shinki Murakami, Mika Takeshima, Natsuko Kumamoto, Asako Sato, Ikuko Miyazaki, Shinsuke Matsuzaki, Toshikuni Sasaoka, Taiichi Katayama, Masato Asanuma

    PLOS ONE   9 ( 5 )   e97918   2014年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PUBLIC LIBRARY SCIENCE  

    In the rodent brain, certain G protein-coupled receptors and adenylyl cyclase type 3 are known to localize to the neuronal primary cilium, a primitive sensory organelle protruding singly from almost all neurons. A recent chemical screening study demonstrated that many compounds targeting dopamine receptors regulate the assembly of Chlamydomonas reinhardtii flagella, structures which are analogous to vertebrate cilia. Here we investigated the effects of dopaminergic inputs loss on the architecture of neuronal primary cilia in the rodent striatum, a brain region that receives major dopaminergic projections from the midbrain. We first analyzed the lengths of neuronal cilia in the dorsolateral striatum of hemi-parkinsonian rats with unilateral lesions of the nigrostriatal dopamine pathway. In these rats, the striatal neuronal cilia were significantly longer on the lesioned side than on the non-lesioned side. In mice, the repeated injection of reserpine, a dopamine-depleting agent, elongated neuronal cilia in the striatum. The combined administration of agonists for dopamine receptor type 2 (D2) with reserpine attenuated the elongation of striatal neuronal cilia. Repeated treatment with an antagonist of D2, but not of dopamine receptor type 1 (D1), elongated the striatal neuronal cilia. In addition, D2-null mice displayed longer neuronal cilia in the striatum compared to wild-type controls. Reserpine treatment elongated the striatal neuronal cilia in D1-null mice but not in D2-null mice. Repeated treatment with a D2 agonist suppressed the elongation of striatal neuronal cilia on the lesioned side of hemi-parkinsonian rats. These results suggest that the elongation of striatal neuronal cilia following the lack of dopaminergic inputs is attributable to the absence of dopaminergic transmission via D2 receptors. Our results provide the first evidence that the length of neuronal cilia can be modified by the lack of a neurotransmitter's input.

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  • Protective Effects of Phytochemical Antioxidants Against Neurotoxin-Induced Degeneration of Dopaminergic Neurons 査読

    Taizo Kita, Masato Asanuma, Ikuko Miyazaki, Mika Takeshima

    JOURNAL OF PHARMACOLOGICAL SCIENCES   124 ( 3 )   313 - 319   2014年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:JAPANESE PHARMACOLOGICAL SOC  

    The specific toxicity to dopaminergic neurons of psychostimulants and neurotoxins has been extensively studied in vivo and in vitro, and findings have been used to establish animal models of amphetamine psychosis or Parkinson's disease. The multiple mechanisms of neurotoxicity operating in these disorders are known to involve oxidative stress or neuroinflammation, producing the characteristic behavioral and neuropathlogical changes arising from injured dopaminergic neurons and glial cells. A number of studies have shown that glia-targeting antioxidants play important roles in protecting against the neurotoxicity caused by psychostimulants or neurotoxins. Phytochemicals, which are non-nutritive plant chemicals, protect dopaminergic neurons and glial cells from damage caused by psychostimulants or neurotoxins. The objective of this review was to evaluate the involvement of glial cells in dopaminergic neuron specific toxicity and to explore the neuroprotective activity of phytochemicals in terms of anti-inflammatory and antioxidant action.

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  • Effects of Bupropion and Pramipexole on Cell Proliferation in the Hippocampus of Adrenocorticotropic Hormone-Treated Rats 査読

    Yuka Onoue, Keiko Kuwatsuka, Ikuko Miyazaki, Masato Asanuma, Yoshihisa Kitamura, Toshiaki Sendo

    BIOLOGICAL & PHARMACEUTICAL BULLETIN   37 ( 2 )   327 - 330   2014年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PHARMACEUTICAL SOC JAPAN  

    The dopamine reuptake inhibitor bupropion and dopamine D2/3 receptor agonist pramipexole have been clinically proven to improve both depression and treatment-resistant depression. We examined its influence on the duration of immobility during the forced swim test in adrenocorticotropic hormone (ACTH)-treated rats and further analyzed the possible role of the dopamine nerve system in this effect. Bupropion and pramipexole significantly decreased the duration of immobility in normal and ACTH-treated rats. We previously demonstrated that the chronic administration of ACTH caused a significant decrease in hippocampal cell proliferation and neurogenesis. In this study, we used the mitotic marker 5-bromo-2'-deoxyridine to investigate the effects of bupropion and pramipexole on cell proliferation in the subgranular zone of the hippocampal dentate gyms following chronic treatment with ACTH. The ACTH treatment for 14 d decreased adult hippocampal cell proliferation. The chronic administration of bupropion for 14 d blocked the loss of cell proliferation resulting from the chronic treatment with ACTH, whereas pramipexole did not. The administration of bupropion may have treatment-resistant antidepressive properties, which may be partly attributed to the normalization of hippocampal cell proliferation.

    DOI: 10.1248/bpb.b13-00749

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  • Metallothionein deficiency exacerbates diabetic nephropathy in streptozotocin-induced diabetic mice 査読

    Hiromi Tachibana, Daisuke Ogawa, Norio Sogawa, Masato Asanuma, Ikuko Miyazaki, Naoto Terami, Takashi Hatanaka, Chikage Sato Horiguchi, Atsuko Nakatsuka, Jun Eguchi, Jun Wada, Hiroshi Yamada, Kohji Takei, Hirofumi Makino

    AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY   306 ( 1 )   F105 - F115   2014年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER PHYSIOLOGICAL SOC  

    Oxidative stress and inflammation play important roles in diabetic complications, including diabetic nephropathy. Metallothionein (MT) is induced in proximal tubular epithelial cells as an antioxidant in the diabetic kidney; however, the role of MT in renal function remains unclear. We therefore investigated whether MT deficiency accelerates diabetic nephropathy through oxidative stress and inflammation. Diabetes was induced by streptozotocin injection in MT-deficient (MT-/-) and MT+/+ mice. Urinary albumin excretion, histological changes, markers for reactive oxygen species (ROS), and kidney inflammation were measured. Murine proximal tubular epithelial (mProx24) cells were used to further elucidate the role of MT under high-glucose conditions. Parameters of diabetic nephropathy and markers of ROS and inflammation were accelerated in diabetic MT-/- mice compared with diabetic MT+/+ mice, despite equivalent levels of hyperglycemia. MT deficiency accelerated interstitial fibrosis and macrophage infiltration into the interstitium in the diabetic kidney. Electron microscopy revealed abnormal mitochondrial morphology in proximal tubular epithelial cells in diabetic MT-/- mice. In vitro studies demonstrated that knockdown of MT by small interfering RNA enhanced mitochondrial ROS generation and inflammation-related gene expression in mProx24 cells cultured under high-glucose conditions. The results of this study suggest that MT may play a key role in protecting the kidney against high glucose-induced ROS and subsequent inflammation in diabetic nephropathy.

    DOI: 10.1152/ajprenal.00034.2013

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  • Transplantation of Melanocytes Obtained from the Skin Ameliorates Apomorphine-Induced Abnormal Behavior in Rodent Hemi-Parkinsonian Models 査読

    Masato Asanuma, Ikuko Miyazaki, Francisco J. Diaz-Corrales, Youichirou Higashi, Masayoshi Namba, Norio Ogawa

    PLoS ONE   8 ( 6 )   e65983   2013年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Tyrosinase, which catalyzes both the hydroxylation of tyrosine and consequent oxidation of L-DOPA to form melanin in melanocytes, is also expressed in the brain, and oxidizes L-DOPA and dopamine. Replacement of dopamine synthesis by tyrosinase was reported in tyrosine hydroxylase null mice. To examine the potential benefits of autograft cell transplantation for patients with Parkinson's disease, tyrosinase-producing cells including melanocytes, were transplanted into the striatum of hemi-parkinsonian model rats or mice lesioned with 6-hydroxydopamine. Marked improvement in apomorphine-induced rotation was noted at day 40 after intrastriatal melanoma cell transplantation. Transplantation of tyrosinase cDNA-transfected hepatoma cells, which constitutively produce L-DOPA, resulted in marked amelioration of the asymmetric apomorphine-induced rotation in hemi-parkinsonian mice and the effect was present up to 2 months. Moreover, parkinsonian mice transplanted with melanocytes from the back skin of black newborn mice, but not from albino mice, showed marked improvement in the apomorphine-induced rotation behavior up to 3 months after the transplantation. Dopamine-positive signals were seen around the surviving transplants in these experiments. Taken together with previous studies showing dopamine synthesis and metabolism by tyrosinase, these results highlight therapeutic potential of intrastriatal autograft cell transplantation of melanocytes in patients with Parkinson's disease. © 2013 Asanuma et al.

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  • Protective effect of cepharanthin on cisplatin-induced renal toxicity through metallothionein expression 査読

    Norio Sogawa, Kanji Hirai, Chiharu Sogawa, Kazumi Ohyama, Ikuko Miyazaki, Goichi Tsukamoto, Masato Asanuma, Akira Sasaki, Shigeo Kitayama

    Life Sciences   92 ( 12 )   727 - 732   2013年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Aims Cisplatin (CDDP) is a potent anticancer agent, but severe renal toxicity can limit its use. We investigated the protective effect of cepharanthin (CE), a biscoclaurin alkaloid, on the renal toxicity of CDDP. Main methods Mice were given CDDP along with CE. Effects of CE on CDDP toxicity were investigated by assaying markers of renal toxicity together with MT expression, and by histopathological examination of the kidney. MT-null mice were also examined. Key findings CE induced expression of metallothionein (MT). Pre-administration of CE attenuated an increase in blood urea nitrogen (BUN) concentrations after the CDDP injection. A histochemical analysis demonstrated protection against CDDP-induced necrocytosis of kidney tissues by CE. The protective effect of CE did not occur in the MT-null mice. Significance Pretreatment with CE may reduce the renal toxicity of CDDP through expression of MT. © 2013 Elsevier Inc.

    DOI: 10.1016/j.lfs.2013.01.031

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  • Effect of the 5-HT1A receptor function on antidepressive effect and neurogenesis in ACTH treated rats 査読

    Miyake Ayaka, Kitamura Yoshihisa, Hattori Sayo, Koyama Toshihiro, Miyazaki Ikuko, Asanuma Masato, Sendo Toshiaki

    JOURNAL OF PHARMACOLOGICAL SCIENCES   121   144P   2013年

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    記述言語:日本語  

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  • Influence of doxorubicin and cyclophosphamide on psychological behavior in rats 査読

    Kitamura Yoshihisa, Hattori Sayo, Miyake Ayaka, Koyama Toshihiro, Miyazaki Ikuko, Asanuma Masato, Sendo Toshiaki

    JOURNAL OF PHARMACOLOGICAL SCIENCES   121   143P   2013年

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    記述言語:日本語  

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  • アストロサイトとParkinson病治療

    浅沼幹人, 宮崎育子

    神経内科   79 ( 2 )   262 - 268   2013年

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  • 培養アストログリア細胞における細胞保護効果.

    喜多大三, 浅沼幹人, 宮崎育子, 竹島美香

    九州栄養福祉大学研究紀要   ( 10 )   179 - 191   2013年

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  • The mechanisms of electroconvulsive stimuli in BrdU-positive cells of the dentate gyrus in ACTH-treated rats 査読

    Keiko Kuwatsuka, Hiromi Hayashi, Yuka Onoue, Ikuko Miyazaki, Toshihiro Koyama, Masato Asanuma, Yoshihisa Kitamura, Toshiaki Sendo

    Journal of Pharmacological Sciences   122 ( 1 )   34 - 41   2013年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    In clinical studies, electroconvulsive stimuli have been associated with improvements in both depression and treatment-resistant depression. In a previous study, treatment with adrenocorticotropic hormone (ACTH) for 14 days decreased adult hippocampal cell proliferation. Furthermore, electroconvulsive stimuli significantly decreased the duration of immobility following repeated administration of ACTH for 14 days in rats. The present study was undertaken to further characterize the mechanism of treatment-resistant antidepressant effects of electroconvulsive stimuli by measuring cell proliferation, brain-derived neurotrophic factor (BDNF) levels, and phosphorylated and total cyclic adenosine monophosphate (cAMP) response element-binding protein (pCREB/CREB) levels in the hippocampus of ACTH-treated rats. Electroconvulsive stimuli increased cell proliferation in both saline-treated and ACTH-treated rats. Mature-BDNF protein levels showed a tendency to decrease in ACTH-treated rats. Electroconvulsive stimuli treatment increased mature-BDNF protein levels in the hippocampus of both saline-treated and ACTH-treated rats. Furthermore, electroconvulsive stimuli increased phospho-Ser133-CREB (pCREB) levels and the ratio of pCREB/CREB in both saline-treated and ACTH-treated rats. These findings suggest that the treatment-resistant antidepressant effects of electroconvulsive stimuli may be attributed, at least in part, to an enhancement of hippocampal cell proliferation. © The Japanese Pharmacological Society.

    DOI: 10.1254/jphs.13015FP

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  • Centrosomal aggregates and Golgi fragmentation disrupt vesicular trafficking of DAT 査読

    Francisco J. Diaz-Corrales, Ikuko Miyazaki, Masato Asanuma, Diego Ruano, Rosa M. Rios

    NEUROBIOLOGY OF AGING   33 ( 10 )   2462 - 2477   2012年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE INC  

    Lewy bodies containing the centrosomal protein gamma-tubulin and fragmentation of Golgi apparatus (GA) have been described in nigral neurons of Parkinson's disease (PD) patients. However, the relevance of these features in PD pathophysiology remains unknown. We analyzed the impact of proteasome inhibition in the formation of gamma-tubulin-containing aggregates as well as on GA structure. SH-SY5Y cells were treated with the proteasome inhibitor Z-Leu-Leu-Leu-al (MG132) to induce centrosomal-protein aggregates. Then, microtubules (MTs) and Golgi dynamics, as well as the vesicular transport of dopamine transporter (DAT) were evaluated both in vitro and in living cells. MG132 treatment induced gamma-tubulin aggregates which altered microtubule nucleation. MG132-treated cells containing gamma-tubulin aggregates showed fragmentation of GA and perturbation of the trans-Golgi network. Under these conditions, the DAT accumulated at the centrosomal-Golgi region indicating that the vesicular transport of DAT was disrupted. Thus, centrosomal aggregates and fragmentation of GA are 2 closely related processes that could result in the disruption of the vesicular transport of DAT toward the plasma membrane in a model of dopaminergic neuronal degeneration. (C) 2012 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.neurobiolaging.2011.11.014

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  • Cyclooxygenase-Independent Neuroprotective Effects of Aspirin Against Dopamine Quinone-Induced Neurotoxicity 査読

    Masato Asanuma, Ikuko Miyazaki, Yuri Kikkawa, Naotaka Kimoto, Mika Takeshima, Shinki Murakami, Ko Miyoshi

    NEUROCHEMICAL RESEARCH   37 ( 9 )   1944 - 1951   2012年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER/PLENUM PUBLISHERS  

    Prostaglandin H synthase exerts not only cyclooxygenase activity but also peroxidase activity. The latter activity of the enzyme is thought to couple with oxidation of dopamine to dopamine quinone. Therefore, it has been proposed that cyclooxygenase inhibitors could suppress dopamine quinone formation. In the present study, we examined effects of various cyclooxygenase inhibitors against excess methyl L-3,4-dihydroxyphenylalanine (L-DOPA)-induced quinoprotein (protein-bound quinone) formation and neurotoxicity using dopaminergic CATH.a cells. The treatment with aspirin inhibited excess methyl L-DOPA-induced quinoprotein formation and cell death. However, acetaminophen did not show protective effects, and indomethacin and meloxicam rather aggravated these methyl L-DOPA-induced changes. Aspirin and indomethacin did not affect the level of glutathione that exerts quenching dopamine quinone in dopaminergic cells. In contrast with inhibiting effects of higher dose in the previous reports, relatively lower dose of aspirin that affected methyl L-DOPA-induced quinoprotein formation and cell death failed to prevent cyclooxygenase-induced dopamine chrome generation in cell-free system. Furthermore, aspirin but not acetaminophen or meloxicam showed direct dopamine quinone-scavenging effects in dopamine-semiquinone generating systems. The present results suggest that cyclooxygenase shows little contribution to dopamine oxidation in dopaminergic cells and that protective effects of aspirin against methyl L-DOPA-induced dopamine quinone neurotoxicity are based on its cyclooxygenase-independent property.

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  • EFFLUENT FREE RADICALS ARE ASSOCIATED WITH RESIDUAL RENAL FUNCTION AND PREDICT TECHNIQUE FAILURE IN PERITONEAL DIALYSIS PATIENTS 査読

    Hiroshi Morinaga, Hitoshi Sugiyama, Tatsuyuki Inoue, Keiichi Takiue, Yoko Kikumoto, Masashi Kitagawa, Shigeru Akagi, Kazushi Nakao, Yohei Maeshima, Ikuko Miyazaki, Masato Asanuma, Makoto Hiramatsu, Hirofumi Makino

    PERITONEAL DIALYSIS INTERNATIONAL   32 ( 4 )   453 - 461   2012年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:MULTIMED INC  

    Objective: Residual renal function (RRF) is associated with low oxidative stress in peritoneal dialysis (PD). In the present study, we investigated the relationship between the impact of oxidative stress on RRF and patient outcomes during PD.
    Methods: Levels of free radicals (FRs) in effluent from the overnight dwell in 45 outpatients were determined by electron spin resonance spectrometry. The FR levels, clinical parameters, and the level of 8-hydroxy-2'-deoxyguanosine were evaluated at study start. The effects of effluent FR level on technique and patient survival were analyzed in a prospective cohort followed for 24 months.
    Results: Levels of effluent FRs showed significant negative correlations with daily urine volume and residual renal Kt/V, and positive correlations with plasma beta(2)-microglobulin and effluent 8-hydroxy-2'-deoxyguanosine. A highly significant difference in technique survival (p &lt; 0.05), but not patient survival, was observed for patients grouped by effluent FR quartile. The effluent FR level was independently associated with technique failure after adjusting for patient age, history of cardiovascular disease, and presence of diabetes mellitus (p &lt; 0.001). The level of effluent FRs was associated with death-censored technique failure in both univariate (p &lt; 0.001) and multivariate (p &lt; 0.01) hazard models. Compared with patients remaining on PD, those withdrawn from the modality had significantly higher levels of effluent FRs (p &lt; 0.005).
    Conclusions: Elevated effluent FRs are associated with RRF and technique failure in stable PD patients. These findings highlight the importance of oxidative stress as an unfavorable prognostic factor in PD and emphasize that steps should be taken to minimize oxidative stress in these patients. Perit Dial Int 2012; 32(4): 453-461

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  • ACTH反復投与ラットにおける海馬細胞新生の減少及びそのメカニズムに関する検討.

    林 宏美, 土居真穂, 尾上由華, 鍬塚圭子, 三宅彩香, 小山敏広, 四宮一昭, 宮崎育子, 浅沼幹人, 北村佳久

    薬学雑誌   173 - 178   2012年

  • テアニンの中枢作用に関する文献的考察.

    喜多大三, 浅沼幹人, 宮崎育子, 竹島美香

    九州栄養福祉大学研究紀要   45 - 58   2012年

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  • Protective effects of baicalein against excess L-DOPA-induced dopamine quinone neurotoxicity 査読

    Mika Takeshima, Maiko Murata, Natsuho Urasoe, Shinki Murakami, Ikuko Miyazaki, Masato Asanuma, Taizo Kita

    NEUROLOGICAL RESEARCH   33 ( 10 )   1050 - 1056   2011年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:MANEY PUBLISHING  

    Objectives: Baicalein, a flavonoid derived from the root of Scutelaria baicalensis Georgi, possesses antioxidative properties including reactive oxygen species scavenging and lipid peroxidation inhibiting activities. The present study was undertaken to investigate the neuroprotective effect of baicalein against dopamine (DA) neurotoxicity induced by exposure to a synthetic DA precursor, L-3,4-dihydroxyphenylalanine (L-DOPA), in cultured dopaminergic CATH. a cells.
    Methods and results: Exposure to L-DOPA for 24 hours reduced the number of viable cells and enhanced protein-bound quinone (quinoprotein) formation in the cell. Both effects were prevented by simultaneous treatment with baicalein. In addition, baicalein prevented the formation of DA semiquinone radicals from DA in an in vitro cell-free system. Long-term baicalein treatment for 96 hours also protected against excess L-DOPA-induced cell death, and also increased glutathione (GSH) levels in CATH. a cells.
    Discussion: Our results indicate that baicalein has neuroprotective properties against excess L-DOPA-induced DA neurotoxicity through the suppression of DA quinone formation. Furthermore, the long-term treatment of baicalein upregulates intracellular GSH contents, which may also exert neuroprotective effects against oxidative stress-induced neuronal damage.

    DOI: 10.1179/1743132811Y.0000000032

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  • Factors That Influence Primary Cilium Length 査読

    Ko Miyoshi, Kyosuke Kasahara, Ikuko Miyazaki, Masato Asanuma

    ACTA MEDICA OKAYAMA   65 ( 5 )   279 - 285   2011年10月

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    記述言語:英語   出版者・発行元:OKAYAMA UNIV MED SCHOOL  

    Almost all mammalian cells carry one primary cilium that functions as a biosensor for chemical and mechanical stimuli. Genetic damages that compromise cilia formation or function cause a spectrum of disorders referred to as ciliapathies. Recent studies have demonstrated that some pharmacological agents and extracellular environmental changes can alter primary cilium length. Renal injury is a well-known example of an environmental insult that triggers cilia length modification. Lithium treatment causes primary cilia to extend in several cell types including neuronal cells; this phenomenon is likely independent of glycogen synthase kinase-3 beta inhibition. In renal epithelial cell lines, deflection of the primary cilia by fluid shear shortens them by reducing the intracellular cyclic AMP level, leading to a subsequent decrease in mechanosensitivity to fluid shear. Primary cilium length is also influenced by the dynamics of actin filaments and microtubules through the levels of soluble tubulin in the cytosol available for primary cilia extension. Thus, mammalian cells can adapt to the extracellular environment by modulating the primary cilium length, and this feedback system utilizing primary cilia might exist throughout the mammalian body. Further investigation is required concerning the precise molecular mechanisms underlying the control of primary cilium length in response to environmental factors.

    DOI: 10.18926/AMO/47009

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  • A Novel Hypothesized Clinical Implication of Zonisamide for Autism Reply

    Masato Asanuma, Ikuko Miyazaki

    ANNALS OF NEUROLOGY   69 ( 2 )   426 - 427   2011年2月

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL  

    DOI: 10.1002/ana.22347

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  • Chronic Treatment with Imipramine and Lithium Increases Cell Proliferation in the Hippocampus in Adrenocorticotropic Hormone-Treated Rats 査読

    Yoshihisa Kitamura, Maho Doi, Keiko Kuwatsuka, Yuka Onoue, Ikuko Miyazaki, Kazuaki Shinomiya, Toshihiro Koyama, Toshiaki Sendo, Hiromu Kawasaki, Masato Asanuma, Yutaka Gomita

    BIOLOGICAL & PHARMACEUTICAL BULLETIN   34 ( 1 )   77 - 81   2011年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PHARMACEUTICAL SOC JAPAN  

    Adult hippocampal neurogenesis is reported to change in animal models of depression and antidepressants. We have used the mitotic marker 5-bromo-2'-deoxyyridine to address the effects of imipramine and lithium on cell proliferation and survival following chronic treatment with adrenocorticotropic hormone (ACTH) in the subgranular zone of the hippocampal dentate gyrus. ACTH treatment for 14d decreased adult hippocampal cell proliferation and survival. Coadministration of imipramine and lithium for 14d blocked the loss of cell proliferation but not cell survival resulting from the chronic treatment with ACTH. The coadministration of imipramine and lithium may have treatment-resistant antidepressive properties, which may be attributed, in part, to a normalization of hippocampal cell proliferation.

    DOI: 10.1248/bpb.34.77

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  • パーキンソン病とアストロサイト─新たな神経保護療法の標的

    浅沼幹人, 宮崎育子

    Clinical Neuroscience   29   1295 - 1297   2011年

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  • L-テアニンのグリア細胞に対する保護作用に関する研究─アストロサイトにおけるL-テアニンによる抗酸化保護作用の賦活─

    喜多大三, 浅沼幹人, 宮崎育子, 竹島美香

    九州栄養福祉大学研究紀要   8   43 - 53   2011年

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  • High glucose increases metallothionein expression in renal proximal tubular epithelial cells. 査読

    Ogawa D, Asanuma M, Miyazaki, I, Tachibana H, Wada J, Sogawa N, Sugaya T, Kitamura S, Maeshima Y, Shikata K, Makino F

    Exp Diabetes Res   2011   1 - 8   2011年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1155/2011/534872

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  • Effects of Imipramine and Lithium on the Suppression of Cell Proliferation in the Dentate Gyrus of the Hippocampus in Adrenocorticotropic Hormone-treated Rats 査読

    Maho Doi, Ikuko Miyazaki, Tomoko Nagamachi, Kazuaki Shinomiya, Hisashi Matsunaga, Toshiaki Sendo, Hiromu Kawasaki, Masato Asanuma, Yutaka Gomita, Yoshihisa Kitamura

    ACTA MEDICA OKAYAMA   64 ( 4 )   219 - 223   2010年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:OKAYAMA UNIV MED SCHOOL  

    We examined the influence of chronic adrenocorticotropic hormone (ACTH) treatment on the number of Ki-67-positive cells in the dentate gyrus of the hippocampus in rats. ACTH treatment for 14 days decreased the number of such cells. The administration of imipramine or lithium alone for 14 days had no effect in saline-treated rats. The effect of ACTH was blocked by the administration of imipramine. Furthermore, the coadministration of imipramine and lithium for 14 days significantly increased the number of Ki-67-positive cells in both the saline and ACTH-treated rats. The coadministration of imipramine and lithium normalized the cell proliferation in the dentate gyrus of the hippocampus in rats treated with ACTH.

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  • Involvement of nicotinic acetylcholine receptor on the conditioned place aversion behavior and c-Fos expression induced by naloxone in single-dose morphine-treated rats 査読

    Ikuta Yuichi, Ishida Shigeru, Miyazaki Ikuko, Asanuma Masato, Araki Hiroaki, Matsunaga Hisashi, Kitamura Yoshihisa, Sendo Toshiaki

    JOURNAL OF PHARMACOLOGICAL SCIENCES   112   187P   2010年

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  • Effects of cell proliferation and astroglial activity by the chronic treatment of ACTH in the hippocampal dentate gyrus of adult rats 査読

    Doi Maho, Nagamachi Tomoko, Egawa Maki, Miyazaki Ikuko, Kawasaki Hiromu, Sendo Toshiaki, Asanuma Masato, Kitamura Yoshihisa

    JOURNAL OF PHARMACOLOGICAL SCIENCES   112   178P   2010年

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  • Pericentrin, a centrosomal protein related to microcephalic primordial dwarfism, is required for olfactory cilia assembly in mice 査読

    Ko Miyoshi, Kyosuke Kasahara, Ikuko Miyazaki, Shoko Shimizu, Manabu Taniguchi, Shinsuke Matsuzaki, Masaya Tohyama, Masato Asanuma

    FASEB JOURNAL   23 ( 10 )   3289 - 3297   2009年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:FEDERATION AMER SOC EXP BIOL  

    The Drosophila pericentrin-like protein has been shown to be essential for the formation of the sensory cilia of chemosensory and mechanosensory neurons by mutant analysis in flies, while the in vivo function of pericentrin, a well-studied mammalian centrosomal protein related to microcephalic primordial dwarfism, has been unclear. To determine whether pericentrin is required for ciliogenesis in mammals, we generated and analyzed mice with a hypomorphic mutation of Pcnt encoding the mouse pericentrin. Immunofluorescence analysis demonstrated that olfactory cilia of chemosensory neurons in the nasal olfactory epithelium were malformed in the homozygous mutant mice. On the other hand, the assembly of motile and primary cilia of non-neuronal epithelial cells and the formation of sperm flagella were not affected in the Pcnt-mutant mice. The defective assembly of olfactory cilia in the mutant was apparent from birth. The mutant animals displayed reduced olfactory performance in agreement with the compromised assembly of olfactory cilia. Our findings suggest that pericentrin is essential for the assembly of chemosensory cilia of olfactory receptor neurons, but it is not globally required for cilia formation in mammals.-Miyoshi, K., Kasahara, K., Miyazaki, I., Shimizu, S., Taniguchi, M., Matsuzaki, S., Tohyama, M., Asanuma, M. Pericentrin, a centrosomal protein related to microcephalic primordial dwarfism, is required for olfactory cilia assembly in mice. FASEB J. 23, 3289-3297 ( 2009). www.fasebj.org

    DOI: 10.1096/fj.08-124420

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  • Lithium treatment elongates primary cilia in the mouse brain and in cultured cells 査読

    Ko Miyoshi, Kyosuke Kasahara, Ikuko Miyazaki, Masato Asanuma

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   388 ( 4 )   757 - 762   2009年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    The molecular mechanisms underlying the therapeutic effects of lithium, a first-line antimanic mood stabilizer, have not yet been fully elucidated. Treatment of the algae Chlamydomonas reinhardtii with lithium has been shown to induce elongation of their flagella, which are analogous structures to vertebrate cilia. In the mouse brain, adenylyl cyclase 3 (AC3) and certain neuropeptide receptors colocalize to the primary cilium of neuronal cells, suggesting a chemosensory function for the primary cilium in the nervous system. Here we show that lithium treatment elongates primary cilia in the mouse brain and in cultured cells. Brain sections from mice chronically fed with Li(2)CO(3) were subjected to immunofluorescence study. Primary cilia carrying both AC3 and the receptor for melanin-concentrating hormone (MCH) were elongated in the dorsal striatum and nucleus accumbens of lithium-fed mice, as compared to those of control animals. Moreover, lithium-treated NIH3T3 cells and cultured striatal neurons exhibited elongation of the primary cilia. The present results provide initial evidence that a psychotropic agent can affect ciliary length in the central nervous system, and furthermore suggest that lithium exerts its therapeutic effects via the upregulation of cilia-mediated MCH sensing. These findings thus contribute novel insights into the pathophysiology of bipolar mood disorder and other psychiatric diseases. (C) 2009 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.bbrc.2009.08.099

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  • Reduction of Nuclear Peroxisome Proliferator-Activated Receptor gamma Expression in Methamphetamine-Induced Neurotoxicity and Neuroprotective Effects of Ibuprofen 査読

    Takeshi Tsuji, Masato Asanuma, Ikuko Miyazaki, Ko Miyoshi, Norio Ogawa

    NEUROCHEMICAL RESEARCH   34 ( 4 )   764 - 774   2009年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER/PLENUM PUBLISHERS  

    We examined changes in nuclear peroxisome proliferator-activated receptor gamma (PPAR gamma) in the striatum in methamphetamine (METH)-induced dopaminergic neurotoxicity, and also examined effects of treatment with drugs possessing PPAR gamma agonistic properties. The marked reduction of nuclear PPAR gamma-expressed cells was seen in the striatum 3 days after METH injections (4 mg/kg x 4, i.p. with 2-h interval). The reduction of dopamine transporter (DAT)-positive signals and PPAR gamma expression, and accumulation of activated microglial cells were significantly and dose-dependently attenuated by four injections of a nonsteroidal anti-inflammatory drug and a PPAR gamma ligand, ibuprofen (10 or 20 mg/kg x 4, s.c.) given 30 min prior to each METH injection, but not by either a low or high dose of aspirin. Either treatment of ibuprofen or aspirin, that showed no effects on METH-induced hyperthermia, significantly blocked the METH-induced striatal cyclooxygenase (COX) expression. Furthermore, the treatment of an intrinsic PPAR gamma ligand 15d-PG J2 also attenuated METH injections-induced reduction of striatal DAT. Therefore, the present study suggests the involvement of reduction of PPAR gamma expression in METH-induced neurotoxicity. Taken together with the previous report showing protective effects of other PPAR gamma ligand, these results imply that the protective effects of ibuprofen against METH-induced neurotoxicity may be based, in part, on its anti-inflammatory PPAR gamma agonistic properties, but not on its COX-inhibiting property or hypothermic effect.

    DOI: 10.1007/s11064-008-9863-x

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  • Effects of dopamine transporter expression on treatment of ACTH in rats 査読

    Emoto Sayaka, Kitamura Yoshihisa, Miyazaki Ikuko, Kitagawa Kouhei, Nagamachi Tomoko, Doi Maho, Ishimaru Yui, Asanuma Masato, Sendo Toshiaki

    JOURNAL OF PHARMACOLOGICAL SCIENCES   109   162P   2009年

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  • Involvement of PPAR-gamma in methamphetamine-induced neurotoxicity and protective effect of interferon-gamma 査読

    Fukuoka Saki, Hozumi Hiroaki, Kimoto Naotaka, Kikkawa Yuri, Tsuji Takeshi, Miyazaki Ikuko, Kitamura Yoshihisa, Sendo Toshiaki, Kita Taizo, Asanuma Masato

    JOURNAL OF PHARMACOLOGICAL SCIENCES   109   220P   2009年

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  • 食材および食品に含まれる化学物質の生理活性とその機能―ドパミン神経培養系におけるフィチン酸の作用―

    浦添 夏帆, 村田 麻衣子, 青柳 東彦, 安東 勢津子, 宮崎 育子, 浅沼 幹人, 喜多 大三

    九州栄養福祉大学研究紀要   6   75 - 86   2009年

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  • DOPAMINE-INDUCED BEHAVIORAL CHANGES AND OXIDATIVE STRESS IN METHAMPHETAMINE-INDUCED NEUROTOXICITY 査読

    Taizo Kita, Ikuko Miyazaki, Masato Asanuma, Mika Takeshima, George C. Wagner

    NEW CONCEPTS OF PSYCHOSTIMULANTS INDUCED NEUROTOXICITY   88   43 - 64   2009年

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    記述言語:英語   掲載種別:論文集(書籍)内論文   出版者・発行元:ELSEVIER ACADEMIC PRESS INC  

    DOI: 10.1016/S0074-7742(09)88003-3

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  • Dopamine Induces Supernumerary Centrosomes and Subsequent Cell Death through Cdk2 up-Regulation in Dopaminergic Neuronal Cells 査読

    Francisco J. Diaz-Corrales, Masato Asanuma, Ikuko Miyazaki, Ko Miyoshi, Nobutaka Hattori, Norio Ogawa

    NEUROTOXICITY RESEARCH   14 ( 4 )   295 - 305   2008年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER  

    Aggregation of proteins in the centrosome is implicated in the pathophysiology of Parkinson&apos;s disease. However, the relevance of the centrosome in neurodegeneration is still obscure. Centrosome duplication is initiated by the cyclin E/cyclin-dependent kinase 2 (Cdk2) complex. The present study determined changes in cyclin E or Cdk2 expression and in the centrosomal structure in dopaminergic neuronal CATH.a cells exposed to 50, 100 and 150 mu M dopamine (DA) for 24 h. DA induced significant increase in Cdk2 protein and cyclin E protein, but not cyclin a mRNA. In DA-treated cells, the intense cyclin E- and Cdk2-immunofluorescence signals were co-localized around large and supernumerary centrosomes, and these two parameters of centrosome amplification were significantly increased compared with the control. Simultaneous co-treatment with DA and a Cdk2 inhibitor blocked centrosome amplification and enhanced cell viability. Our results demonstrated that DA could lead to cyclin E accumulation and Cdk2 up-regulation triggering supernumerary centrosomes and apoptotic cell death.

    DOI: 10.1007/BF03033854

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  • Protective effects of interferon-gamma against methamphetamine-induced neurotoxicity (vol 177, pg 123, 2008) 査読

    Hozumi Hiroaki, Asanuma Masato, Miyazaki Ikuko, Fukuoka Saki, Kikkawa Yuri, Kimoto Naotaka, Kitamura Yoshihisa, Sendo Toshiaki, Kita Taizo, Gomita Yutaka

    TOXICOLOGY LETTERS   180 ( 3 )   231   2008年8月

  • Effects of HMGB1 on ischemia-reperfusion injury in the rat heart 査読

    Susumu Oozawa, Shuji Mori, Toru Kanke, Hideo Takahashi, Keyue Liu, Yasuko Tomono, Masato Asanuma, Ikuko Miyazaki, Masahiro Nishibori, Shunji Sano

    CIRCULATION JOURNAL   72 ( 7 )   1178 - 1184   2008年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:JAPANESE CIRCULATION SOC  

    Background Coronary ischemia-reperfusion (I/R) injury causes cardiomyocyte necrosis in a multi-step process that includes an inflammatory reaction. A recent study has suggested that high-mobility group box 1 (HMGB 1) is a late mediator of lethal sepsis and an early mediator of inflammation and necrosis following I/R injury. In the present study a neutralizing monoclonal antibody (mAb) for HMGB1 was used to clarify the role of HMGB 1 in cardiac I/R injury.
    Methods and Results Rats underwent 30 min of left coronary artery occlusion followed by 60 min reperfusion. An intravenous injection of anti-HMGB1 mAb or control IgG was administered just before reperfusion. The infarct size was enlarged in the anti-HMGB1 mAb group in comparison with the control group (p&lt;0.05). The treatment of anti-HMGB1 mAb significantly increased the plasma troponin-T and norepinephrine (NE) content in the heart in comparison with the control (p&lt;0.05). Moreover, the production of dihydroxyphenylglycol was reduced in the anti-HMGB1-treated group (p&lt;0.05).
    Conclusion This study shows for the first time the effects of treatment with neutralizing anti-HMGB1 mAb on I/R injury in the rat heart. The findings support the novel view that I/R-induced HMGB1 may be an important factor in the modulation of interstitial NE.

    DOI: 10.1253/circj.72.1178

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  • Nonsteroidal anti-inflammatory drugs in experimental parkinsonian models and Parkinson's disease 査読

    Masato Asanuma, Ikuko Miyazaki

    CURRENT PHARMACEUTICAL DESIGN   14 ( 14 )   1428 - 1434   2008年5月

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    記述言語:英語   出版者・発行元:BENTHAM SCIENCE PUBL LTD  

    A number of experimental studies using parkinsonian models have revealed that nonsteroidal anti-inflammatory drugs (NSAIDs) have neuroprotective properties against dopaminergic neurotoxicity not only by their cyclooxygenase-inhibiting effect but also by other specific properties or some unknown pharmacological effects. This article reviews heterogeneous pharmacological properties of NSAIDs including inhibitory effect against nitric oxide synthesis, agonistic action for peroxisome proliferator-activated receptor or possible suppressive effects against dopamine quinone generation, and also reviews their neuroprotective effects in the experimental parkinsonian models and pathogenesis of Parkinson's disease. Several epidemiological studies recently clarified that the use of nonaspirin NSAIDs but not aspirin was associated with a lower prevalence of Parkinson's disease, in contrast with neuroprotective effects of aspirin in the experimental studies. It also discusses the discrepancy between results in the experimental parkinsonian models and epidemiological data in prevalence of Parkinson's disease on the effects of NSAIDs.

    DOI: 10.2174/138161208784480153

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  • [New perspectives on the mechanism of methamphetamine-induced neurotoxicity]. 査読

    Kita T, Takeshima M, Wagner GC, Hozumi H, Miyazaki I, Asanuma M

    Nihon shinkei seishin yakurigaku zasshi = Japanese journal of psychopharmacology   28 ( 2 )   49 - 61   2008年4月

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    記述言語:日本語  

    PubMed

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  • Specific induction of PAG608 in cranial and spinal motor neurons of L-DOPA-treated parkinsonian rats 査読

    Masako Shimizu, Ikuko Miyazaki, Youichirou Higashi, Maria J. Eslava-Alva, Francisco J. Diaz-Coffales, Masato Asanuma, Norio Ogawa

    NEUROSCIENCE RESEARCH   60 ( 4 )   355 - 363   2008年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER IRELAND LTD  

    We identified p53-activated gene 608 (PAG608) as a specifically induced gene in striatal tissue of L-DOPA (100 mg/kg)-injected hemi-parkinsonian rats using differential display assay. In the present study, we further examined morphological distribution of PAG608 in the central nervous system of L-DOPA-treated hemi-parkinsonian rats. PAG608 expression was markedly induced in fibers and neuronal cells of the lateral globus pallidus and reticular thalamic nucleus adjacent to internal capsule, specifically in the parkinsonian side of L-DOPA-treated models. The protein was also constitutively expressed in motor neurons specifically in either side of the pontine nucleus and motor nuclei of trigeminal and facial nerves. Furthermore, L-DOPA-induced PAG608 expression on motor neurons in the contralateral side of the ventral horn of the spinal cord and the lateral corticospinal tract without cell loss. The specific induction of PAG608 6-48 h after L-DOPA injection in the extrapyramidal tracts, pyramidal tracts and corresponding lower motor neurons of the spinal cords suggests its involvement in molecular events in stimulated motor neurons. Taken together with the constitutive expression of PAG608 in the motor nuclei of cranial nerves, PAG608 may be a useful marker of stressed or activated lower motor neurons. (C) 2007 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

    DOI: 10.1016/j.neures.2007.12.006

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  • Protective effects of interferon-gamma against methamphetamine-induced neurotoxicity 査読

    Hiroaki Hozumi, Masato Asanuma, Ikuko Miyazaki, Saki Fukuoka, Yuri Kikkawa, Naotaka Kimoto, Yoshihisa Kitamura, Toshiaki Sendo, Taizo Kita, Yutaka Gomita

    TOXICOLOGY LETTERS   177 ( 2 )   123 - 129   2008年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER IRELAND LTD  

    Repeated injections of methamphetamine (METH) cause degeneration of striatal dopaminergic nerve terminals. In the present study, we examined the effects of interferon-gamma (IFN-gamma) on METH-induced striatal neurotoxicity in mice. Intraperitoneal injection of IFN-gamma before METH injection significantly prevented METH-induced reduction of striatal dopamine transporter (DAT)-positive signals and hyperthermia. Furthermore, intracerebroventricular injection of IFN-gamma before METH treatment markedly prevented METH-induced reduction of DAT. Interestingly, central IFN-gamma injection had no effect on METH-induced hyperthermia. In addition, IFN-gamma injected centrally after METH treatment, but not systemically, 1 h after the final METH injection significantly protected against METH-induced neurotoxicity. Our results suggest that IFN-gamma injected systemically or its related molecule protects against METH-induced neurotoxicity through intracerebral molecular pathways, while it can prevent METH-induced hyperthermia through different molecular events. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

    DOI: 10.1016/j.toxlet.2008.01.005

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  • Biological roles for neuronal primary cilia 査読

    K. Miyoshi, I. Miyazaki, M. Asanuma

    PSYCHIATRY AND CLINICAL NEUROSCIENCES   62 ( 1 )   S6 - S6   2008年2月

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    記述言語:英語   出版者・発行元:BLACKWELL PUBLISHING  

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  • Preventing effects of a novel anti-parkinsonian agent zonisamide on dopamine quinone formation 査読

    Masato Asanuma, Ikuko Miyazaki, Francisco J. Diaz-Corrales, Ko Miyoshi, Norio Ogawa, Miho Murata

    NEUROSCIENCE RESEARCH   60 ( 1 )   106 - 113   2008年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER IRELAND LTD  

    The neurotoxicity of dopamine (DA) quinones as dopaminergic neuron-specific oxidative stress is considered to play a role in the pathogenesis and/or progression of Parkinson's disease (PD), since DA quinones conjugate with several key PD pathogenic molecules (e.g., tyrosine hydroxylase, alpha-synuclein and parkin) to form protein-bound quinone (quinoprotein) and consequently inhibit their functions. Zonisamide (ZNS) is used as an anti-epileptic agent but also improved the cardinal symptoms of PD in recent clinical trials in Japan. To evaluate the effects of ZNS on excess cytosolic free DA-induced quinone toxicity, we examined changes in DA quinone-related indices after ZNS treatment both in in vitro cell-free system and in cultured cells. Co-incubation of DA and ZNS in a cell-free system caused conversion of DA to stable melanin via formation of DA-semiquinone radicals and DA chrome. Long-term (5 days) treatment with ZNS decreased quinoprotein and increased DA/DOPA chromes in dopaminergic CATH.a cells. ZNS significantly inhibited quinoprotein formation induced by treatment with tetrahydrobiopterin and ketanserin that elevate cytosolic free DA in the cells. Our results suggest that the novel anti-parkinsonian agent ZNS possesses preventing effects against DA quinone formation induced by excess amount of cytosolic DA outside the synaptic vesicles. (c) 2007 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

    DOI: 10.1016/j.neures.2007.10.002

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  • Effects of chronic ACTH treatment on astrocytes and neurogenesis in adult rat hippocampus 査読

    Nagamachi Tomoko, Miyazaki Ikuko, Emoto Sayaka, Do Maho, Kawasaki' Hiromu, Asanuma Masato, Kitamura Yoshihisa, Sendo Toshiaki, Gomita Yutaka

    JOURNAL OF PHARMACOLOGICAL SCIENCES   106   188P   2008年

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  • テアニンの培養ドパミン神経およびグリア細胞系への作用

    染矢 恵, 竹島美香, 村田麻衣子, 宮崎育子, 浅沼幹人, 喜多大三

    九州栄養福祉大学研究紀要   5   69 - 81   2008年

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  • 食品および食材に含まれる化学物質のモノアミン神経培養系に及ぼす作用に関する研究

    村田麻衣子, 竹島美香, 染矢 恵, 宮崎育子, 浅沼幹人, 喜多大三

    九州栄養福祉大学研究紀要   5   55 - 67   2008年

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  • メタンフェタミン神経毒性発現に関する研究の新展開

    喜多大三, 竹島美香, Wagner GC, 穂積宏彰, 宮崎育子, 浅沼幹人

    日本神経精神薬理学会雑誌   28   49 - 61   2008年

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  • 小胞外過剰ドパミンによるドパミン神経障害における共通因子としてのキノン体生成

    宮崎育子, 浅沼幹人, Diaz-Corrales FJ, 三好 耕, 小川紀雄

    岡山医学会雑誌   119   235 - 239   2008年

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  • Quinone formation as a common factor for dopamine neuron damages by excessive dopamine outside of vesicles

    Ikuko Miyazaki, Masato Asanuma, Diaz-Corrales FJ, Ko Miyoshi, Norio Ogawa

    Journal of Okayama Medical Association   119 ( 3 )   235 - 239   2008年

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  • Common anti-inflammatory drugs are potentially therapeutic for Parkinson's disease? 査読

    Masato Asanuma, Ikuko Miyazaki

    EXPERIMENTAL NEUROLOGY   206 ( 2 )   172 - 178   2007年8月

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    記述言語:英語   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    DOI: 10.1016/j.expneurol.2007.05.006

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  • Suppression of p53-activated gene, PAG608, attenuates methamphetamine-induced neurotoxicity 査読

    Masato Asanuma, Ikuko Miyazaki, Youichirou Higashi, Francisco J. Diaz-Corrales, Masako Shimizu, Ko Miyoshi, Norio Ogawa

    NEUROSCIENCE LETTERS   414 ( 3 )   263 - 267   2007年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER IRELAND LTD  

    The p53-activated gene 608 (PAG608) is a proapoptotic gene activated and regulated by p53 expression in oxidative stress-induced apoptosis of neuronal cells. In this study, we determined the role of PAG608 in methamphetamine-induced neurotoxicity. Treatment of mouse dopaminergic CATH.a cells with 2 mM methamphetamine increased PAG608 expression at 3 h followed by increase in phosphorylated p53 expression. Transient transfection of PAG608 antisense cDNA or RNA interference using PAG608 small interfering RNA significantly attenuated the dose-dependent decrease in cell viability of CATH.a cells by methamphetamine (1-4 mM) exposure. In monoaminergic neuronal B65 cells, which contain serotonin rather than dopamine, methamphetamine-induced cell death was also significantly but partially protected by transient transfection of PAG608 antisense cDNA. Furthermore, cell death of PC 12 cells produced by methamphetamine (1-5 mM) was almost completely prevented by stable expression of PAG608 antisense cDNA, compared with significant reduction of cell viability in control PC12 cells. Our results showed that suppression of PAG608 using transient and stable transfection with PAG608 anti sense cDNA or small interfering RNA attenuates methamphetamine-induced death of various monoaminergic neuronal cells, suggesting that methamphetamine neurotoxicity in monoaminergic cells is related, at least in part, to induction of PAG608 expression. (c) 2006 Elsevier Ireland Ltd. All rights reserved.

    DOI: 10.1016/j.neulet.2006.12.036

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  • 食品容器および食器より溶出する化学物質のドパミン神経障害性に関する研究-ビスフェノールAの培養ドパミン神経系への作用-

    喜多大三, 竹島美香, 田中弓子, 宮崎育子, 浅沼幹人

    九州栄養福祉大学研究紀要   4   89 - 97   2007年

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  • Involvement of STAT3 in bladder smooth muscle hypertrophy following bladder outlet obstruction

    Osamu Fujita, Masato Asanuma, Teruhiko Yokoyama, Ikuko Miyazaki, Norio Ogawa, Hiromi Kumon

    ACTA MEDICA OKAYAMA   60 ( 6 )   299 - 309   2006年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:OKAYAMA UNIV MED SCHOOL  

    We examined the involvement of the signal transducer and activator of transcription 3 (STAT3) in bladder outlet obstruction (BOO)-induced bladder smooth muscle hypertrophy using a rat in vivo and in vitro study. BOO induced increases in bladder weight and bladder smooth muscle thickness I week after the operation. By using antibody microarrays, 64 of 389 proteins blotted on the array met our selection criteria of an INR value between &gt;= 2.0 and &lt;= 0.5. This result revealed up-regulation of transcription factors, cell cycle regulatory proteins, apoptosis-associated proteins and so on. On the other hand, down-regulation (INR value &lt;= 0.5) of proteins was not found. In a profiling study, we found an increase in the expression of STAT3. A significant increase in nuclear phosphorylated STAT3 expression was confirmed in bladder smooth muscle tissue by immunohistochemistry and Western blot analysis. Cyclical stretch-relaxation (I Hz) at 120% elongation significantly increased the expression of STAT3 and of alpha-smooth muscle actin in primary cultured bladder smooth muscle cells. Furthermore, the blockade of STAT3 expression by the transfection of STAT3 small interfering RNA (siRNA) significantly prevented the stretch-induced increase in alpha-smooth muscle actin expression. These results suggest that STAT3 has an important role in the induction of bladder smooth muscle hypertrophy.

    DOI: 10.18926/AMO/30724

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  • Characterization of pericentrin isoforms in vivo 査読

    Ko Miyoshi, Masato Asanuma, Ikuko Miyazaki, Shinsuke Matsuzaki, Masaya Tohyama, Norio Ogawa

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   351 ( 3 )   745 - 749   2006年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    Pericentrin was first identified as a mouse centrosomal protein and is now referred to as pericentrin A. A larger homologous protein in humans with a C-terminal calmodulin-binding domain was later identified as pericentrin B. Pericentrin has been shown to be one of the key components in ciliogenesis.. but in vivo pericentrin products have remained ambiguous. Here we characterized pericentrin isoforms in mice. Two pericentrin transcripts of 9.5 and 6.9 kb were recognized on the mouse tissue Northern blots, while a cRNA probe for a 5'-terminal sequence shared by pericentrin A and B failed to hybridize to the 6.9-kb message. Two pericentrin cDNAs were identified, which encoded pericentrin B and a novel isoform, pericentrin S, sharing with pericentrin B a C-terminal calmodulin-binding motif. Three pericentrin proteins of 360, 255, and 250 kDa revealed by immunoprecipitation analysis were thought to correspond to pericentrin B, pericentrin S, and an unknown N-terminal product. (c) 2006 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.bbrc.2006.10.101

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  • Embryonic expression of pericentrin suggests universal roles in ciliogenesis 査読

    Ko Miyoshi, Kazunari Onishi, Masato Asanuma, Ikuko Miyazaki, Francisco J. Diaz-Corrales, Norio Ogawa

    DEVELOPMENT GENES AND EVOLUTION   216 ( 9 )   537 - 542   2006年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER  

    Pericentrin (Pcnt) is a giant coiled-coil protein known to mediate microtubule organization. It has been recently reported that mitosis-specific centrosomal anchoring of gamma tubulin complexes by Pcnt acts to control mitotic spindle organization, though little is known about the in vivo expression of Pcnt. In this study, we investigated Pcnt expression in mouse embryos. In situ hybridization analysis revealed preferential expression of Pcnt in quiescent G(0) phase cells throughout the embryo with an unexpectedly low expression level in proliferating cells, suggesting that Pcnt might not play an important role in mitotic proliferation. Immunofluorescence analysis confirmed preferential expression of the Pcnt protein in G(0) phase cells. Moreover, Pcnt was shown to be localized to the base of primary cilia in multiple embryonic tissues, in agreement with a recent study demonstrating the involvement of Pcnt in primary cilia formation using cultured mammalian cells.

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  • Centrosome overduplication induced by rotenone treatment affects the cellular distribution of p53 tumor suppressor protein in the neuroblastoma B65 cell line 査読

    FJ Diaz-Corrales, M Asanuma, Miyazaki, I, K Miyoshi, N Ogawa

    PSYCHIATRY AND CLINICAL NEUROSCIENCES   60   S18 - S26   2006年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BLACKWELL PUBLISHING  

    Recently, the formation of inclusion bodies in several neurodegenerative diseases, including Parkinson's disease, has been associated with the aggregation of unfolded proteins recruited in the centrosome. We have reported previously that rotenone, an insecticide that is used to produce experimental models of Parkinsonism, induced the aggregation of the alpha-synuclein protein in the centrosome, and it notably affected the structure and function of this organelle in primary cultures of mesencephalic neurons and astrocytes. However, it is still obscure the mechanisms through which the disorganization and centrosomal dysfunction could induce cell death. In this study the rat neuroblastoma B65 cell line was chronically exposed to rotenone, and then the distribution of the centrosomal protein gamma-tubulin was studied by immunocytochemistry and Western blot analyses. Finally, the configuration of mitotic spindles and distribution of the p53 protein was observed in the control and rotenone-treated groups. Rotenone treatment increased the number of cells having centrosome overduplication and multipolar mitotic spindles. In contrast, rotenone induced redistribution of the p53 protein, which was colocalized with the gamma-tubulin protein in the perinuclear region of cells having overduplicated centrosomes. In addition, the p53 positive signal was markedly intense in cells containing aberrant chromosome segregation and micronuclei. Our results suggest that centrosome overduplication may play an important role in the redistribution of the p53 protein in rotenone-treated cells, and this could represent an alternative mechanism of rotenone to induce apoptosis in neuronal cells.

    DOI: 10.1111/j.1440-1819.2006.01526.x

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  • Nonsteroidal anti-inflammatory drugs in Parkinson's disease: possible involvement of quinone formation. 査読

    Asanuma, M, Miyazaki, I

    Expert Rev. Neurother.   6   1313 - 1325   2006年

  • L-DOPA treatment from the viewpoint of neuroprotection - Possible mechanism of specific and progressive dopaminergic neuronal death in Parkinson's disease 査読

    N Ogawa, M Asanuma, Miyazaki, I, FJ Diaz-Corrales, K Miyoshi

    JOURNAL OF NEUROLOGY   252   23 - 31   2005年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:DR DIETRICH STEINKOPFF VERLAG  

    With regard to the mechanism of selective dopaminergic neuronal death, experimental results of studies on the neurotoxicity of MPTP and rotenone indicate that degeneration of dopamine neurons is closely related to mitochondrial dysfunction, inflammatory process and oxidative stress, particularly with regard to the generation of quinones as dopamine neuron-specific oxidative stress. Thus, it is now clear that the presence of high levels of discompartmentalized free dopamine in sdopaminergic neurons may explain the specific vulnerability of dopaminergic neurons through the generation of highly toxic quinones.

    DOI: 10.1007/s00415-005-4006-7

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  • Prednisolone inhibits proliferation of cultured pulmonary artery smooth muscle cells of patients with idiopathic pulmonary arterial hypertension

    A Ogawa, K Nakamura, H Matsubara, H Fujio, T Ikeda, K Kobayashi, Miyazaki, I, M Asanuma, K Miyaji, D Miura, KF Kusano, H Date, T Ohe

    CIRCULATION   112 ( 12 )   1806 - 1812   2005年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

    Background - Idiopathic pulmonary arterial hypertension (IPAH) is associated with proliferation of smooth muscle cells (SMCs) in small pulmonary arteries. There is no therapy that specifically inhibits SMC proliferation. Recent studies reported that prednisolone (PSL) inhibits the postangioplasty proliferation of SMCs in atherosclerotic arteries. In this study, we tested the hypothesis that PSL has antiproliferative effects on pulmonary artery SMCs of patients with IPAH.
    Methods and Results - Pulmonary artery SMCs were harvested from the pulmonary arteries of 6 patients with IPAH who underwent lung transplantation. Control SMCs were obtained from 5 patients with bronchogenic carcinoma who underwent lung lobectomy. After incubation in the presence of platelet-derived growth factor ( PDGF), PSL was added at different concentrations and cell proliferation was assessed by H-3-thymidine incorporation. PSL ( 2 x 10(-4) and 2 x 10(-3) mol/L) significantly inhibited PDGF-stimulated proliferation ( P &lt; 0.05) of SMCs from patients with IPAH but did not affect cell viability of SMCs, as confirmed by trypan blue staining. In cell cycle analysis using a microscope-based multiparameter laser scanning cytometer, PSL inhibited the progression of SMCs from G(0)/G(1) to the S phase. This inhibition was associated with increased p27 expression level. PSL ( 2 x 10(-4) mol/L) also inhibited PDGF-induced SMC migration.
    Conclusions - Our results indicate that PSL has an antiproliferative effect on cultured SMCs of pulmonary arteries from patients with IPAH and suggest that PSL may be potentially useful therapeutically in patients with IPAH.

    DOI: 10.1161/CIRCULATIONHA.105.536169

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  • Pramipexole has ameliorating effects on levodopa-induced abnormal dopamine turnover in parkinsonian striatum and quenching effects on dopamine-semiquinone generated in vitro

    M Asanuma, Miyazaki, I, FJ Diaz-Corrales, M Shimizu, K Tanaka, N Ogawa

    NEUROLOGICAL RESEARCH   27 ( 5 )   533 - 539   2005年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:MANEY PUBLISHING  

    Objectives and methods: To clarify the effects of a non-ergot do amine agonist pramipexole on levodopa-induced abnormal dopamine metabolism in the parkinsonian model, we examined striatal changes in dopamine and its metabolites after repeated administration of pramipexole and/or levodopa using 6-hydroxydopamine-lesioned hemi-parkinsonian mice. Moreover, the effects of pramipexole on dopamine-semiquinones were also accessed using an in vitro dopamine-semiquinone generating system to elucidate its neuroprotective property against dopamine quinone-induced neurotoxicity that appears as dopamine neuron-specific oxidative stress.
    Results: Combined administration of pramipexole (0.5 or 1 mg/kg/day, 7 days) selectively suppressed the levodopa-induced (50 mg/kg/day) increase of striatal dopamine turnover in the parkinsonian side, but not in the non-lesioned side. In addition to the antioxidant properties previously reported, it was clarified that pramipexole scavenged dopamine-semiquinones generated in a dose-dependent manner either in simultaneous incubation or post-incubation.
    Discussion: The neurotoxicity of dopamine quinones that appear as dopaminergic neuronspecific oxidative stress has recently been known to play a role in the pathogenesis of Parkinson's disease and neurotoxin-induced parkinsonism. Therefore, the present results revealed that pramipexole possesses neuroprotective effects against abnormal dopamine metabolism in excessively levodopa-administered parkinsonian brains and against cytotoxic dopamine quinones generated from excess dopamine, preventing consequentry dopaminergic neuronal damage induced by excess dopamine or levodopa.

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  • 薬物依存・毒性発現にかかわる分子の分子生物学的検索法─網羅的プロファイリングを中心に.

    浅沼幹人, 宮崎育子

    日本薬理学雑誌   126, 30-34   2005年

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  • Rotenone induces aggregation of gamma-tubulin protein and subsequent disorganization of the centrosome: Relevance to formation of inclusion bodies and neurodegeneration 査読

    FJ Diaz-Corrales, M Asanuma, Miyazaki, I, K Miyoshi, N Ogawa

    NEUROSCIENCE   133 ( 1 )   117 - 135   2005年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    Neurodegenerative disorders are characterized by progressive loss of specific neurons in the central nervous system. Although they have different etiologies and clinical manifestations, most of them share similar histopathologic characteristics such as the presence of inclusion bodies in both neurons and glial cells, which represent intracellular aggregation of misfolded or aberrant proteins. In Parkinson's disease, formation of inclusion bodies has been associated with the aggresome-related process and consequently with the centrosome. However, the significance of the centrosome in the neurodegenerative process remains obscure. In the present study, the morphological and functional changes in the centrosome induced by rotenone, a common insecticide used to produce experimental Parkinsonism, were examined both in vitro and in vivo. Aggregation of gamma-tubulin protein, which is a component of the centrosome matrix and recently identified in Lewy bodies of Parkinson's disease, was observed in primary cultures of mesencephalic cells treated with rotenone. Rotenone-treated neurons and astrocytes showed enlarged and multiple centro-somes. These centrosomes also displayed multiple aggregates of alpha-synuclein protein. Neurons with disorganized centrosomes exhibited neurite retraction and microtubule destabilization, and astrocytes showed disturbances of mitotic spindles. The Golgi apparatus, which is closely related to the centrosome, was dispersed in both rotenone-treated neuronal cells and the substantia nigra of rotenone-treated rats. Our findings suggested that recruitment of abnormal proteins in the centrosome contributed to the formation of inclusion bodies, and that rotenone markedly affected the structure and function of the centrosome with consequent induction of cytoskeleton disturbances, disassembly of the Golgi apparatus and collapse of neuronal cells. (c) 2005 IBRO. Published by Elsevier Ltd. All rights reserved.

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  • Quinone formation as dopaminergic neuron-specific oxidative stress in the pathogenesis of sporadic Parkinson's disease and neurotoxin-induced parkinsonism 査読

    M Asanuma, Miyazaki, I, FJ Diaz-Corrales, N Ogawa

    ACTA MEDICA OKAYAMA   58 ( 5 )   221 - 233   2004年10月

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    記述言語:英語   出版者・発行元:OKAYAMA UNIV MED SCHOOL  

    Parkinson's disease (PD) is a progressive neurodegenerative disease characterized by dopaminergic neuron-specific degeneration in the substantia, nigra. A number of gene mutations and deletions have been reported to play a role in the pathogenesis of familial PD. Moreover, a number of pathological and pharmacological studies on sporadic PD and dopaminergic neurotoxin-induced parkinsonism have hypothesized that mitochondrial dysfunction, inflammation, oxidative stress, and dysfunction of the ubiquitin-proteasome system all play important roles in the pathogenesis and progress of PD. However, these hypotheses do not yet fully explain the mechanisms of dopaminergic neuron-specific cell loss in PD. Recently, the neurotoxicity of dopamine quinone formation by auto-oxidation of dopamine has been shown to cause specific cell death of dopaminergic neurons in the pathogenesis of sporadic PD and dopaminergic neurotoxin-induced parkinsonism. Furthermore, this quinone formation is closely linked to other representative hypotheses in the pathogenesis of PD. In this article, we mainly review recent studies on the neurotoxicity of quinone formation as a dopaminergic neuron-specific oxidative stress and its role in the etiology of PD, in addition to several neuroprotective approaches against dopamine quinone-induced toxicity.

    DOI: 10.18926/AMO/32105

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  • Expression of metallothionein-III and cell death in differentiated catecholaminergic neuronal cells 査読

    Y Higashi, M Asanuma, Miyazaki, I, N Ogawa

    NEUROLOGICAL RESEARCH   26 ( 6 )   671 - 676   2004年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:MANEY PUBLISHING  

    Metallothionein (MT)-III, an isomer of metallothionein, is also known to be a growth inhibitory factor. MT-III has been reported to decrease the number of surviving neuronal cells in culture medium containing brain extract. Using differentiated catecholaminergic neuronal CATH.a cells treated with dibutyryl cyclic AMP, we examined MT-III expression and the effect of mouse forebrain extract on cell viability. Increase in MT-III expression was revealed in the differentiated cells. Moreover, treatment with mouse forebrain extract induced apoptotic cell death in differentiated CATH.a cells, accompanied by decreases in both MT-III and a neuronal differentiation marker, growth-associated protein-43, expression in surviving cells. These results imply that MT-III expression during the developmental period may be associated with the regulation of normal neural differentiation.

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  • Parkin attenuates manganese-induced dopaminergic cell death 査読

    Y Higashi, M Asanuma, Miyazaki, I, N Hattori, Y Mizuno, N Ogawa

    JOURNAL OF NEUROCHEMISTRY   89 ( 6 )   1490 - 1497   2004年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BLACKWELL PUBLISHING LTD  

    Manganese as environmental factor is considered to cause parkinsonism and induce endoplasmic reticulum stress-mediated dopaminergic cell death. We examined the effects of manganese on parkin, identified as the gene responsible for familial Parkinson's disease, and the role of parkin in manganese-induced neuronal cell death. Manganese dose-dependently induced cell death of dopaminergic SH-SY5Y and CATH.a cells and cholinergic Neuro-2a cells, and that the former two cell types were more sensitive to manganese toxicity than Neuro-2a cells. Moreover, manganese increased the expression of endoplasmic reticulum stress-associated genes, including parkin, in SH-SY5Y cells and CATH.a cells, but not in Neuro-2a cells. Treatment with manganese resulted in accumulation of parkin protein in SH-SY5Y cells and its redistribution to the perinuclear region, especially aggregated Golgi complex, while in Neuro-2a cells neither expression nor redistribution of parkin was noted. Manganese showed no changes in proteasome activities in either cell. Transient transfection of parkin gene inhibited manganese- or manganese plus dopamine-induced cell death of SH-SY5Y cells, but not of Neuro-2a cells. Our results suggest that the attenuating effects of parkin against manganese- or manganese plus dopamine-induced cell death are dopaminergic cell-specific compensatory reactions associated with its accumulation and redistribution to perinuclear regions but not with proteasome system.

    DOI: 10.1111/j.1471-4159.2004.02445.x

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  • DISC1 localizes to the centrosome by binding to kendrin 査読

    K Miyoshi, M Asanuma, Miyazaki, I, FJ Diaz-Corrales, T Katayama, M Tohyama, N Ogawa

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   317 ( 4 )   1195 - 1199   2004年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    Disrupted-In-Schizophrenia 1 (DISC1) was identified as a novel gene disrupted by a (1; 11)(q42.1;q 14.3) translocation that segregated with major mental disorders in a Scottish family. Using the yeast two-hybrid system, we screened a human brain cDNA library for interactors of the DISC1 protein. One of the positive clones encoded kendrin/pericentrin-B, a giant protein known to localize specifically to the centrosome. The interaction between DISCI and kendrin in mammalian cells was demonstrated by an immunoprecipitation assay. Residues 446-533 of DISC1 were essential for the interaction with kendrin. Immunocytochemical analysis revealed the colocalization of DISC1 and kendrin to the centrosome. These data indicate that DISC1 localizes to the centrosome by binding to kendrin. Kendrin has been reported to anchor the gamma-tubulin complex to the centrosome, providing microtubule nucleation sites. The present study suggests the possible involvement of DISC1 in the pathophysiology of mental disorders due to its putative effect on centrosomal function. (C) 2004 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.bbrc.2004.03.163

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  • Rotenone induces disassembly of the Golgi apparatus in the rat dopaminergic neuroblastoma B65 cell line 査読

    FJ Diaz-Corrales, M Asanuma, Miyazaki, I, N Ogawa

    NEUROSCIENCE LETTERS   354 ( 1 )   59 - 63   2004年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCI IRELAND LTD  

    It has been reported that the Golgi apparatus (GA) is fragmented in some neurodegenerative diseases. However, the significance of the GA fragmentation or disassembly in neurodegeneration is still obscure. To clarify the involvement of this organelle in apoptosis of neuronal cells, we examined the morphological changes in the GA induced by rotenone, a pesticide that produces selective dopaminergic neurodegeneration. In dopaminergic neuroblastoma B65 cells, a 5-day rotenone treatment (50 nM) promoted cell damage. Rotenone-treated cells showed round nuclei, diffuse signals of the GA and cytosolic redistribution of cytochrome c. Nevertheless, these type of cells without nuclear fragmentation did not show any caspase-3 expression. These results indicate that rotenone induces disassembly of the GA in the early stages of the apoptotic process. (C) 2003 Elsevier Ireland Ltd. All rights reserved.

    DOI: 10.1016/j.neulet.2003.09.059

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  • 実験的パーキンソニズムに使われる薬剤〜MPTP,6-ヒドロキシドパミンならびにロテノン.

    浅沼幹人, 宮崎育子, 小川紀雄

    医薬ジャーナル   40,111-116   2004年

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  • 遺伝子改変によるパーキンソン病モデル.

    浅沼幹人, 宮崎育子

    脳の科学   292,165-170   2004年

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  • ドパミン受容体とトランスポーター.

    小川紀雄, 宮崎育子

    脳の科学   292,53-59   2004年

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  • Neuroprotective effects of nonsteroidal anti-inflammatory drugs on neurodegenerative diseases 査読

    M Asanuma, Miyazaki, I, N Ogawa

    CURRENT PHARMACEUTICAL DESIGN   10 ( 6 )   695 - 700   2004年

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    記述言語:英語   出版者・発行元:BENTHAM SCIENCE PUBL LTD  

    It is well known that nonsteroidal anti-inflammatory drugs (NSAIDs) possess anti-inflammatory, analgesic and antipyretic properties by inhibiting cyclooxygenase (COX), a prostaglandin-synthesizing enzyme. It has also been revealed that NSAIDs exert inhibitory effects on the generating system of nitric oxide radicals and modulating effects on transcription factors which are related to inflammatory reactions including cytokine expression. Recently, a number of studies have been conducted focusing on the neuroprotective effects of NSAIDs, since it has been reported that inflammatory processes are associated with the pathogenesis of several neurodegenerative diseases including Alzheimer's disease and Parkinson's disease. In the experimental model of Parkinson's disease, NSAIDs have also exerted neuroprotective effects which are based not only on their COX-inhibiting effects but also on other properties: inhibitory effects on nitric oxide synthesis, action as agonists for peroxisome proliferator-activated receptor gamma, and some unknown pharmacological effects. In this article, various pharmacological effects of NSAIDs except their inhibitory action on COX are reviewed, and possible neuroprotective effects of NSAIDs have been discussed on neurodegenerative diseases, especially Parkinson's disease.

    DOI: 10.2174/1381612043453072

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  • Specific gene expression and possible involvement of inflammation in methamphetamine-induced neurotoxicity 査読

    M Asanuma, Miyazaki, I, Y Higashi, T Tsuji, N Ogawa

    CURRENT STATUS OF DRUG DEPENDENCE / ABUSE STUDIES: CELLULAR AND MOLECULAR MECHANISMS OF DRUGS OF ABUSE AND NEUROTOXICITY   1025   69 - 75   2004年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NEW YORK ACAD SCIENCES  

    To reveal specific gene expression in methamphetamine (METH) -induced dopamine neurotoxicity, temporal characteristics of METH-induced changes in gene expression in dopaminergic neuronal cells were examined using the cDNA array and the differential display method. A number of genes in the class of "trafficking & protein turnover," "metabolic pathways," "transmitters & receptors," and "growth factors, cytokines" were upregulated after the METH treatment in the eDNA array assay. Whereas, some genes related to trafficking & protein turnover and "modulators, effectors & intracellular transducers" were decreased by METH. Some proteins associated with synaptic vesicle transportation indeed up- or downregulated after the METH treatment. These data suggest that the protein trafficking and degradation system is involved in the dopaminergic cell death induced by METH. Furthermore, focusing on inflammatory reactions after METH injection, possible neuroprotective property of nonsteroidal anti-inflammatory drugs were examined against METH-induced neurotoxicity. Coadministration of NSAID with METH significantly attenuated striatal dopamine terminal degeneration and microgliosis induced by METH, suggesting that the protective effects are based on their inhibitory activity on production of cytokines and nitric oxides or their suppressive action against microglia activation.

    DOI: 10.1196/annals.1316.009

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  • Methamphetamine-induced neurotoxicity in mouse brain is attenuated by ketoprofen, a non-steroidal anti-inflammatory drug 査読

    M Asanuma, T Tsuji, Miyazaki, I, K Miyoshi, N Ogawa

    NEUROSCIENCE LETTERS   352 ( 1 )   13 - 16   2003年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCI IRELAND LTD  

    We examined effects of non-steroidal anti-inflammatory drugs (NSAIDs) on methamphetamine (METH)-induced neurotoxicity. Marked reduction of dopamine transporter-positive signals and accumulation of microglial cells in the striatum after METH injections (4 mg/kg x 4, i.p. with 2 h-interval) were significantly and dose-dependently attenuated by four injections of ketoprofen (2 or 5 mg/kg X 4, s.c.) given 30 min prior to each METH injection, but not by either a low or high dose of aspirin. The present results suggest that the protective effects of ketoprofen against METH-induced neurotoxicity and microgliosis might be based on its inhibitory activity on inflammatory response or on microglia activation, but not on its cyclooxygenase-inhibiting property. This provides a possible new strategy against METH-induced neurotoxicity using commonly used NSAIDs. (C) 2003 Elsevier Ireland Ltd. All rights reserved.

    DOI: 10.1016/S0304-3940(03)01001-2

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  • Overexpression of Cu-Zn superoxide dismutase protects neuroblastoma cells against dopamine cytotoxicity accompanied by increase in their glutathione level 査読

    ME Haque, M Asanuma, Y Higashi, Miyazaki, I, K Tanaka, N Ogawa

    NEUROSCIENCE RESEARCH   47 ( 1 )   31 - 37   2003年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCI IRELAND LTD  

    Dopamine (DA) was shown to exert toxic effects on cultured neurons through autoxidation or oxidative deamination, followed by formation of highly reactive quinone compounds and superoxide radicals. In the present study, therefore, any involvement of Cu-Zn superoxide dismutase (SOD) in DA toxicity was evaluated by transfection of Cu-Zn SOD cDNA. The transient transfection of Cu-Zn SOD cDNA inhibited the DA-induced decrease of dopaminergic neuroblastoma cells. Moreover, Cu-Zn SOD cDNA-transfection significantly increased the glutathione (GSH) level when the cells were exposed to DA. However, such Cu-Zn SOD-overexpression failed to show any protective effects against hydrogen peroxide. The Cu-Zn SOD-overexpressing cells also showed significantly higher levels of GSH upon DA exposure than did the empty vector-transfected cells. The increase in the GSH level in response to hydrogen peroxide remained almost identical in empty vector-transfected or Cu-Zn SOD-overexpressed cells. The level of GSH in DA-treated Cu-Zn SOD-overexpressing cells was 2.5-fold higher than that increased by hydrogen peroxide exposure. The catechol structure of DA molecule is probably involved in the mechanism of increasing GSH level. Furthermore, the Cu-Zn SOD-overexpressing cells inhibited the activation of caspase-3 upon DA exposure. Therefore, Cu-Zn SOD overexpression may temporarily inhibit or delay DA autoxidation and consequently increase the GSH level, which then prevents the activation of apoptotic pathway and subsequent cell death. (C) 2003 Elsevier Science Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

    DOI: 10.1016/S0168-0102(03)00166-4

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  • Apoptosis-inducing neurotoxicity of dopamine and its metabolites via reactive quinone generation in neuroblastoma cells 査読

    ME Haque, M Asanuma, Y Higashi, Miyazaki, I, K Tanaka, N Ogawa

    BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS   1619 ( 1 )   39 - 52   2003年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE BV  

    Neurotoxic properties Of L-dopa and dopamine (DA)-related compounds were assessed in human neuroblastoma SH-SY5Y cells with reference to their structural relationship. L-Dopa and its metabolites containing two free hydroxyl residues on their benzene ring showed toxicity in the cell, which was prevented by superoxide dismutase (SOD) and reduced glutathione (GSH), but not by catalase. Furthermore, a synthetic derivative of DA, 3-hydroxy-4-methoxyphenethylamine (HMPE) containing methoxy residue at position 4 in the benzene ring, exerted partial cytotoxicity, which was not prevented by SOD, GSH or catalase. However, the metabolites containing methoxy residue at position 3 failed to show a toxic effect in the SH-SY5Y cells. Moreover, DA induced apoptotic cell death, which was observed by nuclear and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining and measurement of caspase-3 activity; this compound up-regulated apoptotic factor p53 while down-regulating anti-apoptotic factor Bcl-2. In the cell-free in vitro electron spin resonance (ESR) spectrometry, DA possessing two hydroxyl groups showed generation of DA-semiquinone radicals, which were markedly prevented by addition of SOD or GSH but not by catalase. On the other hand, methylation of one of the hydroxyl residues on the benzene ring of DA converted DA to an unoxidizable compound (3-MT or HMPE), and caused it to lose the property to produce serniquinione radicals. It has been previously reported that SOD acting as a superoxide: semiquitione oxidoreductase prevents quinone formation, and that reduced GSH through forming a complex with DA-quinone prevents quinone binding to the thiol group of the intact protein. Therefore, the present results suggest that DA and its metabolites containing two hydroxyl residues exert cytotoxicity mainly due to generation of highly reactive quinones. (C) 2002 Elsevier Science B.V. All rights reserved.

    DOI: 10.1016/S0304-4165(02)00440-3

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  • アルツハイマー病脳で減少しているgrowth inhibitory factor (GIF) の加齢にともなう変化.

    浅沼幹人, 宮崎育子, 東 洋一郎, 田中健一, 小川紀雄

    分子精神医学   2003年

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  • ドパミンおよびその誘導体のキノン体生成を介したアポトーシス誘導性.

    浅沼幹人, 宮崎育子, Haque ME, 東 洋一郎, 小川紀雄

    Prog Med   2003年

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  • 非ステロイド性消炎鎮痛薬の神経保護作用の新展開.

    浅沼幹人, 宮崎育子, 辻 武史, 小川紀雄

    日本神経精神薬理学会雑誌   23,111-119   2003年

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  • Dopamine- or L-DOPA-induced neurotoxicity: The role of dopamine quinone formation and tyrosinase in a model of Parkinson's disease 査読

    M Asanuma, Miyazaki, I, N Ogawa

    NEUROTOXICITY RESEARCH   5 ( 3 )   165 - 176   2003年

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    記述言語:英語   出版者・発行元:F P GRAHAM PUBLISHING CO  

    Dopamine (DA)- or L-dihydroxyphenylalanine- (L-DOPA-) induced neurotoxicity is thought to be involved not only in adverse reactions induced by long-term L-DOPA therapy but also in the pathogenesis of Parkinson!s disease. Numerous in vitro and in vivo studies concerning DA- or L-DOPA-induced neurotoxicity have been reported in recent decades. The reactive oxygen or nitrogen species generated in the enzymatical oxidation or auto-oxidation of an excess amount of DA induce neuronal damage and/or apoptotic or non-apoptotic cell death; the DA-induced damage is prevented by various intrinsic and extrinsic antioxidants. DA and its metabolites containing two hydroxyl residues exert cytotoxicity in dopaminergic neuronal cells mainly due to the generation of highly reactive DA and DOPA quinones which are dopaminergic neuron-specific cytotoxic molecules. DA and DOPA quinones may irreversibly alter protein function through the formation of 5-cysteinyl-catechols on the proteins. For example, the formation of DA quinone-alpha-synuclein consequently increases cytotoxic protofibrils and the covalent modification of tyrosine hydroxylase by DA quinones. The melanin-synthetic enzyme tyrosinase in the brain may rapidly oxidize excess amounts of cytosolic DA and L-DOPA, thereby preventing slowly progressive cell damage by auto-oxidation of DA, thus maintaning DA levels. Since tyrosinase also possesses catecholamine-synthesizing activity in the absence of tyrosine hydroxylase (TH), the double-edged synthesizing and oxidizing functions of tyrosinase in the dopaminergic system suggest its potential for application in the synthesis of DA, instead of TH in the degeneration of dopaminergic neurons, and in the normalization of abnormal DA turnover in long-term L-DOPA-treated Parkinson's disease patients.

    DOI: 10.1007/BF03033137

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  • The p53-activated gene, PAG608, requires a zinc finger domain for nuclear localization and oxidative stress-induced 査読

    Y Higashi, M Asanuma, Miyazaki, I, ME Haque, N Fujita, K Tanaka, N Ogawa

    JOURNAL OF BIOLOGICAL CHEMISTRY   277 ( 44 )   42224 - 42232   2002年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC  

    The p53-activated gene PAG608, which encodes a nuclear zinc finger protein, is a p53-inducible gene that contributes to p53-mediated apoptosis. However, the mechanisms by which PAG608 is involved in the apoptosis of neuronal cells are still obscure. In this study, we demonstrated that expression of p53 was induced by 100 muM 6-hydroxydopamine (6-OHDA), accompanied by increased PAG608 expression in PC12 cells. On the other hand, transient or permanent transfection of antisense PAG608 cDNA into PC12 cells significantly prevented apoptotic cell death induced by 100 muM 6-OHDA or 200 muM hydrogen peroxide but not by 250 muM 1-methyl-4phenylpyridinium ion. The 6-OHDA-induced activation of caspase-3, DNA fragmentation, loss of mitochondria membrane potential, and induction of p53 and Bax were also prevented in PC12 cells that stably expressed antisense PAG608 cDNA. These results suggest that PAG608 is associated with the apoptotic pathway induced by these oxidative stress-generating reagents, upstream of the collapse in the mitochondrial membrane potential in PC12 cells. Interestingly, transient transfection with PAG608 cDNA increased p53 expression in both PC12 cells and B65 cells, indicating that PAG608 induced by p53 is able to induce p53 expression in these cells inversely. Furthermore, transient transfection of a truncated mutant PAG608 cDNA, lacking the first zinc finger domain, inhibited 6-OHDA-induced cell death and altered the nuclear and nucleolar localization of wild-type PAG608 in PC12 cells. These results suggest that PAG608 may induce or regulate p53 expression and translocate to the nucleus and nucleolus using its first zinc finger domain during oxidative stress-induced apoptosis of catecholamine-containing cells.

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  • Aggravation of 6-hydroxydopamine-induced dopaminergic lesions in metal lothionein-I and -II knock-out mouse brain 査読

    M Asanuma, Miyazaki, I, Y Higashi, K Tanaka, ME Haque, N Fujita, N Ogawa

    NEUROSCIENCE LETTERS   327 ( 1 )   61 - 65   2002年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCI IRELAND LTD  

    The effects of two major isoforms of metallothioneins (MTs), MT-I and -II, on dopaminergic neurotoxicity of 6-hydroxydopamine (6-OHDA) were examined using intracerebroventricularly 6-OHDA-injected MT-I, II knock-out (KO) mice. The loss of dopamine neurons in the substantia nigra pars compacta induced by the 6-OHDA injection was significantly aggravated in the MT-I, II KO mice, compared with that in the 6-OHDA-injected wild-type mice. The present results, taken together with the antioxidant properties of MT-I and -II suggest that MT-I and -II exert neuroprotective effects against the dopaminergic neurotoxicity of 6-OHDA at the nigral cell body by scavenging free radicals. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

    DOI: 10.1016/S0304-3940(02)00346-4

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  • The dopamine agonist cabergoline provides neuroprotection by activation of the glutathione system and scavenging free radicals 査読

    M Yoshioka, K Tanaka, Miyazaki, I, N Fujita, Y Higashi, M Asanuma, N Ogawa

    NEUROSCIENCE RESEARCH   43 ( 3 )   259 - 267   2002年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCI IRELAND LTD  

    Free radicals are involved in the pathogenesis and/or progression of Parkinson's disease (PD). Several ergot derivative dopamine (DA) agonists have been reported to scavenge free radicals in vitro and to show a neuroprotective effect in vivo. We investigated the in vitro free radical scavenging and antioxidant activities of cabergoline, a long-acting ergot DA agonist, as well as its ability to activate glutathione (GSH), catalase (Cat) and superoxide dismutase (SOD) activating effects and its in vivo neuroprotective properties against 6-hydroxydopamine (6-OHDA) intracerebroventricularly (i.c.v.) in mice. The striatal DA turnover induced by i.c.v. injection of 6-OHDA was completely normalized by pretreatment with cabergoline. Moreover, cabergoline scavenged free radicals in vitro and significantly reduced lipid peroxidation in vitro and in vivo. Furthermore, daily administration of cabergoline to mice significantly increased striatal GSH levels by activation of RNA expressions of GSH-related enzymes, although striatal Cat and SOD activities did not change. In addition, our present results suggest that repeated administration of cabergoline attenuates both 6-OHDA-induced nigrostriatal DAergic dysfunction and DA neuronal cell death, since cabergoline also had a neuroprotective effect in the immunohistochemical experiment. In conclusion, our findings indicate that the multiple antioxidant mechanisms of cabergoline, such as activation of the GSH system and the direct free radical scavenging activity, may explain the neuroprotective effect of this ergot DA agonist. (C) 2002 Elsevier Science Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

    DOI: 10.1016/S0168-0102(02)00040-8

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  • Methamphetamine-induced increase in striatal p53 DNA-binding activity is attenuated in Cu,Zn-superoxide dismutase transgenic mice 査読

    M Asanuma, Miyazaki, I, Y Higashi, JL Cadet, N Ogawa

    NEUROSCIENCE LETTERS   325 ( 3 )   191 - 194   2002年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCI IRELAND LTD  

    The striatal DNA-binding activities of p53 as a transcription factor were gradually increased at several days after a single methamphetamine (METH) injection, while they were more rapidly increased within several hours after repeated METH injections (x 4 with a 2 h interval). The elevation of striatal p53 DNA-binding after repeated METH injections was markedly attenuated in Cu,Zn-superoxide dismutase transgenic mice, but not affected by treatments with N-methyl-Daspartate or D1 receptor antagonists. The present results suggest that METH-induced production of reactive oxygen species activates striatal p53 DNA-binding activity; this, in turn, may activate other downstream pathways that are responsible for chronic neurotoxicity of METH. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

    DOI: 10.1016/S0304-3940(02)00291-4

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  • Chronic cerebral hypoperfusion induces striatal alterations due to the transient increase of NO production and the depression of glutathione content 査読

    K Tanaka, N Wada-Tanaka, Miyazaki, I, M Nomura, N Ogawa

    NEUROCHEMICAL RESEARCH   27 ( 4 )   331 - 336   2002年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:KLUWER ACADEMIC/PLENUM PUBL  

    We examined the effects of chronic cerebral hypoperfusion on the endogenous oxidative stress-related indices, nitrite and nitrate (NOx) concentration. glutathione (GSH) content, superoxide dismutase and catalase activities, and thiobarbituric acid-reactive substances level in the rat striatum, to clarify the participation of oxidative stress in the chronic cerebral hypoperfusion-induced alterations. Our present results indicate that chronic cerebral hypoperfusion produces oxidative stress and disturbs intracellular redox regulation in two distinct phases: at I day, "acute" and at 6 weeks, "chronic" alterations after the operation, Therefore, striatal neural cell damage may be mainly attributed to the transient increase of NOx production at I day after, and the delayed reduction of muscarinic acetylcholine receptor binding in the striatum may be mostly attributed to the continuous depression of GSH content from the 1st to the 6th postoperative week. In particular, the continuous GSH depression may be considered to accompany the pathophysiology of chronic cerebral hypoperfusion.

    DOI: 10.1023/A:1014967414468

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  • GPI1046 prevents dopaminergic dysfunction by activating glutathione system in the mouse striatum 査読

    K Tanaka, M Yoshioka, Miyazaki, I, N Fujita, N Ogawa

    NEUROSCIENCE LETTERS   321 ( 1-2 )   45 - 48   2002年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCI IRELAND LTD  

    We investigated both the antioxidant activities of GPI1046, a non-immunosuppressive derivative of FK506, and the in vivo neuroprotective properties against toxicity of intracerebroventricular 6-hydroxydopamine (6-OHDA) in mice. The 6-OHDA-induced reduction in dopamine and its metabolites in the striatum was significantly normalized by daily administration of GPI1046. Moreover, GPI1046 significantly reduced lipid peroxidation in vivo. Further, GPI1046 significantly increased striatal glutathione (GSH) levels by activating GSH synthesis, although the striatal catalase and superoxide dismutase activities did not change. We conclude that GPI1046 may have neuroprotective effects both in cell cultures and in vivo. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

    DOI: 10.1016/S0304-3940(01)02547-2

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  • ニューロメラニン合成酵素チロシナーゼのドパミン神経障害への関与.

    浅沼幹人, 東 洋一郎, 宮崎育子, 小川紀雄

    Prog Med   2002年

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  • Neuroprotective effects of non-steroidal anti-inflammatory drugs by direct scavenging of nitric oxide radicals 査読

    M Asanuma, S Nishibayashi-Asanuma, Miyazaki, I, M Kohno, N Ogawa

    JOURNAL OF NEUROCHEMISTRY   76 ( 6 )   1895 - 1904   2001年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BLACKWELL SCIENCE LTD  

    Recently, it has been reported that inflammatory processes are associated with the pathophysiology of Alzheimer's disease and that treatment of non-steroidal anti-inflammatory drugs reduce the risk for Alzheimer's disease. in the present study, we examined nitric oxide radical quenching activity of non-steroidal anti-inflammatory drugs;and steroidal drugs using our established direct in vitro nitric oxide radical detecting system by electron spin resonance spectrometry. The non-steroidal anti-inflammatory drugs, aspirin, mefenamic acid, indomethacin and ketoprofen directly and dose-dependently scavenged generated nitric oxide radicals, in experiments of nitric oxide radical donor, NOC18-induced neuronal damage, these four non-steroidal drugs significantly prevented the NOC18-induced reduction of cell viability and apoptotic nuclear changes in neuronal cells without affecting the induction of inducible nitric oxide synthase-like immunoreactivity. However, ibuprofen, naproxen or steroidal drugs, which had less or no scavenging effects in vitro showed almost no protective effects against NOC18-induced cell toxicity. These results suggest that the protective effects of the former four non-steroidal anti-inflammatory drugs against apoptosis might be mainly due to their direct nitric oxide radical scavenging activities in neuronal cells. These direct NO quenching activities represent novel effects of nonsteroidal anti-inflammatory drugs. Our findings identified novel pharmacological mechanisms of these drugs to exert not only their anti-inflammatory, analgesic, antipyretic activities but also neuroprotective activities against neurodegeneration.

    DOI: 10.1046/j.1471-4159.2001.00205.x

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  • Progressive cortical atrophy after forebrain ischemia in diabetic rats 査読

    F Kondo, M Asanuma, Miyazaki, I, Y Kondo, K Tanaka, H Makino, N Ogawa

    NEUROSCIENCE RESEARCH   39 ( 3 )   339 - 346   2001年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCI IRELAND LTD  

    The morphological changes in the brain of diabetic rats were examined up to 8 weeks after transient forebrain ischemia produced by transient occlusion of both carotid arteries. Using histochemistry, we also examined the extent and rate of development of atrophic changes in the brain, appearance of astrocytes, activated microglia, and glucose transporter 1 (GLUT1) in streptozotocin-treated rat brains after forebrain ischemia. Atrophic changes appeared in the hippocampus in both non-diabetic- and diabetic-ischemic groups 4 weeks after ischemia. In diabetic-ischemic rats, the atrophic changes were more severe and progressed more rapidly in the hippocampus, and were also observed in the frontal, temporal and parietal cortices, but not in any cortical areas of the non-diabetic-ischemic rats and non-ischemic-diabetic rats. We observed reduced density of GLUT1 in all corticaI regions and hippocampus in ischemic-diabetic rats at 4-8 weeks, when the number of activated microglias and astroglias increased in all cortical regions. Although severe atrophic changes were observed in the gray matter, no serious injury was noted in the white matter in the diabetic-ischemic group. Our results indicate that brain ischemia in the presence of diabetes causes more severe late-onset damage culminating in brain atrophy, compared with non-diabetics. (C) 2001 Elsevier Science Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

    DOI: 10.1016/S0168-0102(00)00233-9

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  • Localization, regulation, and function of metallothionein-III/growth inhibitory factor in the brain 査読

    CA Sogawa, M Asanuma, N Sogawa, Miyazaki, I, T Nakanishi, H Furuta, N Ogawa

    ACTA MEDICA OKAYAMA   55 ( 1 )   1 - 9   2001年2月

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    記述言語:英語   出版者・発行元:OKAYAMA UNIV MED SCHOOL  

    The metallothionein (MT) family is a class of low molecular, intracellular, and cysteine-rich proteins with a high affinity for metals. Although the first of these proteins was discovered nearly 40 years ago, their functional significance remains obscure, Four major isoforms (MT-I, MT-II, MT-III, and MT-IV) have been identified in mammals. MT-I and MT-II are ubiquitously expressed in various organs including the brain, while expression of MT-III and MT-IV is restricted in specific organs. MT-III was detected predominantly in the brain, and characterized as a central nervous system-specific isomer, The role of MTs in the central nervous system has become an intense focus of scientific research. An isomer of MTs, MT-III, of particular interest, was originally discovered as a growth inhibitory factor, and has been found to be markedly reduced in the brain of patients with Alzheimer's disease and several other neurodegenerative diseases, MT-III fulfills unique biological roles in homeostasis of the central nervous system and in the etiology of neuropathological disorders.

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  • Molecular mechanism in activation of glutathione system by ropinirole, a selective dopamine D2 agonist 査読

    K Tanaka, Miyazaki, I, N Fujita, ME Haque, M Asanuma, N Ogawa

    NEUROCHEMICAL RESEARCH   26 ( 1 )   31 - 36   2001年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:KLUWER ACADEMIC/PLENUM PUBL  

    We have previously reported that ropinirole, a non-ergot dopamine agonist, has neuroprotective effects against h-hydroxydopamine in mice based on in vivo antioxidant properties such as the glutathione (GSH)-activating effect. In the present study, we determined that the effects of ropinirole on the level of expression of GSH-related enzyme mRNA, these enzymes were shown to regulate GSH contents in the brain. This study focused on the mechanism of GSH enhancement by ropinirole. Striatal GSH contents were significantly increased by 7-day daily administration of ropinirole. Furthermore, the expression levels of gamma -glutamylcysteine synthetase (gamma -GCS), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione S-transferase (GST) mRNA increased following daily injections of ropinirole for 7 days. In addition, ropinirole treatment for 7 days suppressed auto-oxidation in mouse striatal homogenates, in contrast to the vehicle treatment. In conclusion, ropinirole was able to suppress auto-oxidation, most probably by increasing GSH levels due to an increase of GSH synthesis. In addition, it is likely that auto-oxidation was also suppressed by the activation of GSH-regulating enzymes such as GPx, GR, and GST in the mouse striatum. Thus, our results indicate that the GSH-activating effect of ropinirole may render this dopamine agonist beneficial as a neuroprotective drug.

    DOI: 10.1023/A:1007672414239

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  • Inhibition of tyrosinase reduces cell viability in catecholaminergic neuronal cells 査読

    Y Higashi, M Asanuma, Miyazaki, I, N Ogawa

    JOURNAL OF NEUROCHEMISTRY   75 ( 4 )   1771 - 1774   2000年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

    The biosynthesis of dopamine (DA) in catecholaminergic neurons is regulated by tyrosine hydroxylase, which converts tyrosine into 3,4-dihydroxyphenylalanine (L-DOPA). In melanocytes, tyrosinase catalyzes both the hydroxylation of tyrosine and the consequent oxidation of L-DOPA to form melanin. Although ii has been demonstrated that tyrosinase is also expressed in the brain. the physiological role of tyrosinase in the brain is stilt obscure. In this study. to investigate the role of tyrosinase in catecholaminergic neuronal cells, we examined the effects of tyrosinase inhibition on the viability of CATH,a and SH-SY5Y cells using tyrosinase inhibitors-specifically, phenylthiourea (PTU) and 5-hydroxyindole (5-HI)-and the transfection of antisense tyrosinase cDNA. Both inhibitors significantly reduced the cell viability of CATH.a cells in a dose-dependent manner. PTU also specifically enhanced DA-induced cell death, but 5-HI did not. This discrepancy in cell death is probably due to the inhibitors' different mechanism of action: 5-HI inhibits the hydroxylation or tyrosine as a competitor for the substrate to induce cell death that may be due to depletion of DA, whereas PTU mainly inhibits the enzymatic oxidation of L-DOPA and DA rather than tyrosine hydroxylation to increase consequently autooxidation of DA. Indeed. the intracellular DA content in CATH.a cells was enhanced by PTU exposure. In contrast, PTU showed no enhancing effects on DA-induced cell death of SH-SY5Y cells, which express little tyrosinase. Furthermore. transfection with antisense tyrosinase cDNA into CATH.a cells dramatically reduced cell viability and significantly enhanced DA-induced cell death. These results suggest that tyrosinase controls the intracellular DA content by biosynthesis or enzymatic oxidation of DA, and the dysfunction of this activity induces cell death by elevation of intracellular DA level and consequent gradual autooxidation of DA to generate reactive oxygen species.

    DOI: 10.1046/j.1471-4159.2000.0751771.x

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  • Antioxidants protect against dopamine-induced metallothionein-III (GIF) mRNA expression in mouse glial cell line (VR-2g) 査読

    CA Sogawa, Miyazaki, I, N Sogawa, M Asanuma, N Ogawa, H Furuta

    BRAIN RESEARCH   853 ( 2 )   310 - 316   2000年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE BV  

    Metallothionein (MT)-III, originally discovered as a growth inhibitory factor (GIF), is a brain specific isomer of MTs and is markedly reduced in the brain of patients with Alzheimer's disease (AD) or other neurodegenerative diseases. We analyzed the level and regulation of mRNA expression of MT-III in immortalized fetal mouse brain glial cells (VR-2g) by reverse transcriptase-polymerase chain reaction (RT-PCR). We have recently reported that dopamine (DA) increases the expression of MT-III mRNA in vitro. In this study, we investigated the mechanism of such increase by examining the effects of DA agonists (SKF38393 or bromocriptine) and DA antagonists (SCH23390 or sulpiride) on the expression of MT-III mRNA. MT-III mRNA did not change by either agonist and DA-increased MT-III mRNA was not inhibited by either antagonist. These results suggested that the induction of MT-III mRNA by DA was not mediated by stimulation of DA receptors. On the other hand, DA-induced MT-III mRNA expression was strongly inhibited by the addition of antioxidants (glutathione, vitamin E or ascorbic acid), indicating thar DA-enhanced MT-III mRNA was mediated by reactive oxygen species. Our results suggest that oxidative stress may be one of the principle factors that modulate MT-III mRNA expression. (C) 2000 Elsevier Science B.V. All rights reserved.

    DOI: 10.1016/S0006-8993(99)02284-2

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  • Dopamine D2 receptor-mediated antioxidant and neuroprotective effects of ropinirole, a dopamine agonist 査読

    M Iida, Miyazaki, I, K Tanaka, H Kabuto, E Iwata-Ichikawa, N Ogawa

    BRAIN RESEARCH   838 ( 1-2 )   51 - 59   1999年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE BV  

    Recent information suggests that free radicals are closely involved in the pathogenesis and/or progression of Parkinson's disease (PD). High-dose levodopa therapy has been suggested to increase oxidative stress, thereby accelerating the progression of PD. Based on this viewpoint, free radical scavenging, antioxidant and neuroprotective agents which may prevent the progression of PD have recently attracted considerable attention. For example, ergot derivative dopamine (DA) agonists have been reported to scavenge free radicals in vitro and show a neuroprotective effect in vivo. Non-ergot DA agonists have also recently been used in the treatment of PD despite the lack of substantial evidence for any free radical scavenging activity or antioxidant activity. The present study was conducted to assess the in vitro free radical scavenging and antioxidant activities of ropinirole, a non-ergot DA agonist, as well as its glutathione (GSH), catalase and superoxide dismutase (SOD) activating effects and neuroprotective effect in vivo. Ropinirole scavenges free radicals and suppresses lipid peroxidation in vitro, but these activities are very weak, suggesting that the antioxidant effect of ropinirole observed in vitro may be a minor component of its neuroprotective effect in vivo. Administration of ropinirole for 7 days increased GSH, catalase and SOD activities in the striatum and protected striatal dopaminergic neurons against 6-hydroxydopamine (6-OHDA) in mice. Pre-treatment with sulpiride prevented ropinirole from enhancing striatal GSH, catalase and SOD activities and abolished the protection of dopaminergic neurons against 6-OHDA. Our findings indicate that activation of GSH, catalase and SOB mediated via DA D2 receptors may be the principal mechanism of neuroprotection by ropinirole. (C) 1999 Elsevier Science B.V. All rights reserved.

    DOI: 10.1016/S0006-8993(99)01688-1

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  • Early treatment with cyclosporin A ameliorates the reduction of muscarinic acetylcholine receptors in gerbil hippocampus after transient forebrain ischemia 査読

    Y Kondo, M Asanuma, E Iwata, F Kondo, Miyazaki, I, N Ogawa

    NEUROCHEMICAL RESEARCH   24 ( 1 )   9 - 13   1999年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:KLUWER ACADEMIC/PLENUM PUBL  

    Recent evidence has suggested that cyclosporin A (CsA), an immunosuppressive agent, has neuroprotective properties. However, its mechanisms associated with this activity remain unclear. We have previously shown that post-ischemic administration of CsA daily for 14 days prevented the decrease of muscarinic acetylcholine receptor binding in the hippocampus in the gerbil model of 5-min transient forebrain ischemia. In the present study, CsA (5 mg/kg, subcutaneously) was administered to each animal just after, 2 and 6 h after ischemia so as not to exert its immunosuppressive effect. Initial CsA treatment significantly restored the declined muscarinic acetylcholine receptor binding of the hippocampus 14 days after ischemia similar to the previous report. However, CsA. did not alter reactive changes of astrocytes and microglia in the CA1 area of the hippocampus, which had been suppressed by daily administration. These results indicate that CsA could positively modulate the hippocampal acetylcholine neurotransmission system broken down through the ischemia-induced pyramidal cell death and its action mechanism may have no relation to the immunosuppressive properties.

    DOI: 10.1023/A:1020915727119

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  • Glial cells protect neurons against oxidative stress via transcriptional up-regulation of the glutathione synthesis 査読

    Emi Iwata-Ichikawa, Yoichi Kondo, Ikuko Miyazaki, Masato Asanuma, Norio Ogawa

    Journal of Neurochemistry   72 ( 6 )   2334 - 2344   1999年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    We examined the effects of oxidative stress on rat cultured mesencephalic neurons and glial cells. Glial cells were more resistant to 6- hydroxydopamine (6-OHDA) and H2O2 toxicity than neurons. In glial cells, incubation with 6-OHDA and H2O2 induced a significant increase in the expression of γ-glutamylcysteine synthetase (the rate-limiting enzyme in glutathione synthesis) mRNA, which correlated well with increased TPA- response element (TRE)-binding activity. Furthermore, a subsequent elevation in cellular total glutathione content was also observed. In neurons, both agents decreased TRE-binding activity, and these cells failed to up-regulate the glutathione synthesis. We also examined the mechanisms of the neuroprotective effects of glial cells using a gila conditioned medium. Neurons maintained in gila conditioned medium up-regulated the level of TRE- binding activity, γ-glutamylcysteine synthetase mRNA expression, and total glutathione content in response to 6-OHDA or H2O2, and became more resistant to both agents than cells maintained in a normal medium. Neurons maintained in normal medium failed to up-regulate the glutathione synthesis. Our results suggest that transcriptional up-regulation of glutathione synthesis in glial cell appears to mediate brain glial cell resistance against oxidative stress, and that glial cells protect neurons via transcriptional up-regulation of the antioxidant system.

    DOI: 10.1046/j.1471-4159.1999.0722334.x

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  • Protective effects of nicergoline against hydrogen peroxide toxicity in rat neuronal cell line 査読

    E Iwata, Miyazaki, I, M Asanuma, A Iida, N Ogawa

    NEUROSCIENCE LETTERS   251 ( 1 )   49 - 52   1998年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCI IRELAND LTD  

    We examined the effects of nicergoline on hydrogen peroxide (H2O2)-induced neurotoxicity in cultured rat neuronal cell line (B50). H2O2 induced death of B50 cells in a dose-dependent manner. The H2O2-induced neuronal cell death was significantly decreased in B50 cells maintained in the presence of nicergoline. We compared the levels of antioxidants (glutathione, catalase and superoxide dismutase) in nicergoline-treated and untreated B50 cells. Lipid peroxidation products (thiobarbituric acid reactive substances, TEARS) levels were also measured. Cultures treated with nicergoline had higher levels of catalase activity. TEARS level was significantly lower in nicergoline-treated cells than in untreated cells. Our results suggest that nicergoline may induce the up-regulation of intracellular antioxidant defences and protect the neuronal cells against oxidative stress. (C) 1998 Elsevier Science ireland Ltd. All rights reserved.

    DOI: 10.1016/S0304-3940(98)00489-3

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  • Effects of repeated cyclosporin A administration on iminodipropionitrile-induced dyskinesia and TRE-/CRE-binding activities in rat brain 査読

    K Iida, E Iwata, M Asanuma, SN Asanuma, M Gomez-Vargas, Miyazaki, I, T Nakanishi, N Ogawa

    NEUROSCIENCE RESEARCH   30 ( 2 )   185 - 193   1998年2月

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    記述言語:英語   出版者・発行元:ELSEVIER SCI IRELAND LTD  

    To clarify the involvement of immunophilin ligands in the pathogenesis and pathophysiology of dyskinesia, we examined the effects of repeated administration of cyclosporin A (CsA) on rat dyskinesia induced by repeated injection of iminodipropionitrile (IDPN 100 mg/kg, i.p., for 7 days). The addition of CsA treatment (5 mg/kg, s.c., 1 h before each IDPN injection) exacerbated IDPN-induced dyskinesia. In the group treated with both CsA and IDPN, the concentration of dopamine was significantly increased in the striatum and nucleus accumbens compared with the group treated with IDPN alone. Furthermore, in the electrophoretic mobility shift assay, the injection of CsA + IDPN increased binding activities of transcription factors to the TPA (12-O-tetradecanoylphorbol-13-acetate)-responsive element (TRE) and to the cAMP response element (CRE) in the striatum and nucleus accumbens, compared with those in rats treated with IDPN alone. The levels of D-1-receptor mRNA in the striatum were significantly decreased in the IDPN-treated rats but were at the control level in the rats given CsA + IDPN. These findings suggest that the behavioral aggravation of the IDPN-induced dyskinesia caused by CsA administration may be due to the acceleration of the pre- and post-synaptic dopaminegic systems via activation of transcription factors which bind upstream to tyrosine hydroxylase and D-1-receptor genes, and that the immunophilin binding agents such as CsA are involved in this aggravated dyskinesia. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.

    DOI: 10.1016/S0168-0102(97)00128-4

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  • Aniracetam ameriorates impaired pre-and post-synaptic cholinergic indices in gerbil hippocampus induced by transient forebrain ischemia. 査読

    Kondo, Y, Asanuma, M, Kabuto, H, Iwata, E, Kondo, F, Miyazaki, I, Ogawa, N

    J. Brain Sci.   23   250 - 260   1997年

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書籍等出版物

  • アストロサイトの亜鉛関連分子を標的としたパーキンソン病治療戦略

    宮崎育子, 浅沼幹人

    日本薬理学雑誌  2021年 

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  • パーキンソン病での神経保護標的としてのアストロサイトの抗酸化分子

    浅沼幹人, 宮崎育子

    日本薬理学雑誌  2021年 

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  • パーキンソン病と亜鉛結合蛋白

    浅沼幹人, 宮崎育子( 範囲: 生命金属ダイナミクス)

    エヌ・ティー・エス  2021年 

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  • 金属結合蛋白とパーキンソン病

    宮崎育子

    NEURODIEM JAPAN  2020年 

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  • 脳内環境辞典 Nrf2.

    メディカルドウ  2017年 

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  • アストロサイトの部位特異的プロファイルがもたらす脳内環境と神経保護

    浅沼幹人, 宮崎育子( 担当: 共著)

    メディカルドウ  2014年 

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  • Handbook of Free Radicals: Formation, Types and Effects

    Nova Science Publishers  2010年 

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  • 実践行動薬理学

    金芳堂  2010年 

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  • 酸化ストレス─フリーラジカル医学生物学の最前線 Ver.2

    医歯薬出版  2006年 

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MISC

  • 部位特異的アストロサイト機能不全がもたらすロテノン誘発ドパミン神経障害

    宮崎 育子, 浅沼 幹人, 村上 真樹, 菊岡 亮, 磯岡 奈未, 十川 千春, 十川 紀夫, 北村 佳久

    パーキンソン病・運動障害疾患コングレスプログラム・抄録集   13回   118 - 118   2019年7月

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    記述言語:日本語   出版者・発行元:Movement Disorder Society of Japan (MDSJ)  

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  • 大学院生が期待するウェットからドライな薬学研究の未来 抗がん剤投与による不安症状の発症機序解明とその治療・予防に向けたアプローチ

    住吉 佑介, 内藤 七海, 中村 優花, 菅 詩歩, 牛尾 聡一郎, 宮崎 育子, 浅沼 幹人, 北村 佳久, 千堂 年昭

    日本薬学会年会要旨集   139年会 ( 1 )   329 - 329   2019年3月

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    記述言語:日本語   出版者・発行元:(公社)日本薬学会  

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  • ロチゴチンによるアストロサイトのセロトニン1Aレセプターを標的としたドパミン神経保護

    宮崎 育子, 磯岡 奈未, 菊岡 亮, 和田 晃一, 中山 恵利香, 進 浩太郎, 山本 大地, 北村 佳久, 浅沼 幹人

    パーキンソン病・運動障害疾患コングレスプログラム・抄録集   12回   117 - 117   2018年7月

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    記述言語:日本語   出版者・発行元:Movement Disorder Society of Japan (MDSJ)  

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  • Neuroprotective effect of fermented papaya preparation by activation of Nrf2 pathway in astrocytes

    Shinki Murakami, Ikuko Miyazaki, Masato Asanuma

    Nutritional Neuroscience   21 ( 3 )   176 - 184   2018年3月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:Taylor and Francis Ltd.  

    Objectives: Nuclear factor erythroid 2-related factor (Nrf2) in astrocyte plays important roles in brain homeostasis. Fermented papaya preparation (FPP) has anti-oxidative, anti-inflammatory, immunoregulatory properties. The present study investigated the effects of FPP on activation of Nrf2 and release of Nrf2-regulated neuroprotective antioxidants and detoxifying molecules. Methods: Primary cultured astrocytes from rat embryos were treated with FPP for 6 or 24 hours. The expression levels of nuclear Nrf2 and cytoplasmic Nrf2-regulated molecules were determined by western blot analysis and immunohistochemistry. Glutathione levels were measured in cells and medium. Dopaminergic neurons were exposed 6-hydroxydopamine (6-OHDA) with/without pre-treatment with FPP astrocytes. Mice were treated orally with FPP for 2 weeks. Results: FPP increased nuclear translocation of Nrf2 in striatal astrocytes, induced up-regulation of NAD(P)H quinine oxidoreductase-1, glutathione-S transferase and hemeoxygenase-1, and increased glutathione level and the percentage of metallothionein-expressing astrocytes. Moreover, FPP suppressed 6-OHDA-induced dopaminergic neuronal loss in not only neuron-astrocyte mixed culture, but also neuron-rich cultures pre-treated with glial conditioned medium. Two-week oral treatment of mice with FPP resulted in Nrf2 activation and increase in glutathione level in striatum. Discussion: The results indicated that FPP enhances the anti-oxidative capacity through activation of Nrf2 in astrocytes, suggesting it may provide neuroprotection in oxidative stress-related neurodegenerative diseases.

    DOI: 10.1080/1028415X.2016.1253171

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  • 医療のさらなる安心・安全を志向する若手研究者のイノベーティブチャレンジ 抗がん剤投与による不安症状発症の病態機序解明 セロトニン神経系の関与

    中村 優花, 住吉 佑介, 内藤 七海, 牛尾 聡一郎, 宮崎 育子, 浅沼 幹人, 北村 佳久, 千堂 年昭

    日本薬学会年会要旨集   138年会 ( 1 )   333 - 333   2018年3月

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    記述言語:日本語   出版者・発行元:(公社)日本薬学会  

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  • 医療のさらなる安心・安全を志向する若手研究者のイノベーティブチャレンジ 抗がん剤投与による不安症状発症の病態機序解明 セロトニン神経系の関与

    中村 優花, 住吉 佑介, 内藤 七海, 牛尾 聡一郎, 宮崎 育子, 浅沼 幹人, 北村 佳久, 千堂 年昭

    日本薬学会年会要旨集   138年会 ( 1 )   333 - 333   2018年3月

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    記述言語:日本語   出版者・発行元:(公社)日本薬学会  

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  • 農薬ロテノン暴露による腸管神経障害とコーヒー成分による神経保護効果

    宮崎 育子, 磯岡 奈未, 菊岡 亮, 和田 晃一, 北村 佳久, 浅沼 幹人

    パーキンソン病・運動障害疾患コングレスプログラム・抄録集   11回   99 - 99   2017年10月

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    記述言語:日本語   出版者・発行元:Movement Disorder Society of Japan (MDSJ)  

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  • 農薬ロテノンによるアストロサイト機能異常がもたらすドパミン神経障害

    宮崎 育子, 菊岡 亮, 磯岡 奈未, 北村 佳久, 浅沼 幹人

    日本生物学的精神医学会・日本神経精神薬理学会合同年会プログラム・抄録集   39回・47回   158 - 158   2017年9月

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    記述言語:日本語   出版者・発行元:日本生物学的精神医学会・日本神経精神薬理学会  

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  • アストロサイトを介したミルタザピンのドパミン神経保護効果に関する検討

    菊岡 亮, 宮崎 育子, 久保田 菜月, 前田 恵実, 香川 大樹, 守山 雅晃, 粂 明日香, 北村 佳久, 浅沼 幹人

    日本生物学的精神医学会・日本神経精神薬理学会合同年会プログラム・抄録集   39回・47回   193 - 193   2017年9月

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    記述言語:日本語   出版者・発行元:日本生物学的精神医学会・日本神経精神薬理学会  

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  • 農薬ロテノンによる非細胞自律性ドパミン神経障害

    宮崎 育子, 村上 真樹, 菊岡 亮, 磯岡 奈未, 北村 佳久, 浅沼 幹人

    The Journal of Toxicological Sciences   42 ( Suppl. )   S321 - S321   2017年6月

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    記述言語:日本語   出版者・発行元:(一社)日本毒性学会  

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  • Influence of nicotine on doxorubicin and cyclophosphamide combination treatment-induced spatial cognitive impairment and anxiety-like behavior in rats

    Yoshihisa Kitamura, Erika Kanemoto, Misaki Sugimoto, Ayumi Machida, Yuka Nakamura, Nanami Naito, Hirotaka Kanzaki, Ikuko Miyazaki, Masato Asanuma, Toshiaki Sendo

    NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY   390 ( 4 )   369 - 378   2017年4月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:SPRINGER  

    In the present study, we examined the effects of nicotine on cognitive impairment, anxiety-like behavior, and hippocampal cell proliferation in rats treated with a combination of doxorubicin and cyclophosphamide. Combined treatment with doxorubicin and cyclophosphamide produced cognitive impairment and anxiety-like behavior in rats. Nicotine treatment reversed the inhibition of novel location recognition induced by the combination treatment. This effect of nicotine was blocked by methyllycaconitine, a selective alpha 7 nicotinic acetylcholine receptor (nAChR) antagonist, and dihydro-beta-erythroidine, a selective alpha 4 beta 2 nAChR antagonist. In addition, nicotine normalized the amount of spontaneous alternation seen during the Y-maze task, which had been reduced by the combination treatment. This effect of nicotine was inhibited by dihydro-beta-erythroidine. In comparison, nicotine did not affect the anxiety-like behavior induced by the combination treatment. Furthermore, the combination treatment reduced the number of proliferating cells in the subgranular zone of the hippocampal dentate gyrus, and this was also prevented by nicotine. Finally, the combination of doxorubicin and cyclophosphamide significantly reduced hippocampal alpha 7 nAChR mRNA expression. These results suggest that nicotine inhibits doxorubicin and cyclophosphamide-induced cognitive impairment via alpha 7 nAChR and alpha 4 beta 2 nAChR, and also enhances hippocampal neurogenesis.

    DOI: 10.1007/s00210-016-1338-z

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  • 革新的創薬・育薬を目指す若手研究者によるトランスレーショナルリサーチの最前線 パーキンソン病モデルマウスにおけるミルタザピンの神経保護効果に関する検討

    菊岡 亮, 宮崎 育子, 浅沼 幹人, 北村 佳久, 千堂 年昭

    日本薬学会年会要旨集   137年会 ( 1 )   284 - 284   2017年3月

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    記述言語:日本語   出版者・発行元:(公社)日本薬学会  

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  • Therapeutic strategy of targeting astrocytes for neuroprotection in parkinson’s disease

    Ikuko Miyazaki, Masato Asanuma

    Current Pharmaceutical Design   23 ( 33 )   4936 - 4947   2017年

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:Bentham Science Publishers B.V.  

    Parkinson’s disease (PD) is one of common neurodegenerative diseases, which shows motor symptoms including tremor, bradykinesia, rigidity and postural instability. It also involves non-motor symptoms such as cognitive impairment, mental manifestation, autonomic disorder and sensory disturbance. Although treatments to improve the motor disability in PD are being assessed at present, the main challenge remains that is the development of neuroprotective or disease-modifying treatments. Therefore, it is desirable to find approaches that can inhibit the progression of dopaminergic neurodegeneration. Astrocytes are known to play an important role in the maintenance of the neuronal environment and exert neuroprotective effects. Additionally, astrocyte dysfunction increases the susceptibility of neurons to cytotoxicity. We have demonstrated neuroprotective approaches in parkinsonian models in various studies targeting astrocytes. In this article, we summarize the neuroprotective function of astrocytes in the brain, involvement of astrocyte dysfunction in neurodegeneration, and experimental approaches to dopaminergic neuroprotection. We review findings reported in several papers including our own studies. We also address target molecules and pivotal pathways in astrocytes for dopaminergic neuroprotection. The review discusses new promising therapeutic strategies to prevent dopaminergic neurodegeneration in PD.

    DOI: 10.2174/1381612823666170710163731

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  • Editorial: Astrocyte-targeted therapeutic strategies for neurological disorders.

    Miyazaki I

    Curr. Pharm. Des.   23 ( 33 )   4933 - 4935   2017年

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    記述言語:日本語   掲載種別:研究発表ペーパー・要旨(国際会議)  

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  • ALSモデルの運動障害および運動神経変性に対するセロトニン1Aアゴニストの抑制効果

    浅沼幹人, 宮崎育子, 村上真樹, 村上真樹, 鳥越菜央, 中野剛志, 菊岡亮, 北村佳久, 千堂年昭

    パーキンソン病・運動障害疾患コングレスプログラム・抄録集   10th   68 - 68   2016年10月

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    記述言語:日本語   出版者・発行元:Movement Disorder Society of Japan (MDSJ)  

    J-GLOBAL

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  • 農薬ロテノン暴露によるドパミン神経障害におけるアストロサイトの関与

    宮崎育子, 村上真樹, 村上真樹, 菊岡亮, 磯岡奈未, 北村佳久, 浅沼幹人

    パーキンソン病・運動障害疾患コングレスプログラム・抄録集   10th   69 - 69   2016年10月

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    記述言語:日本語   出版者・発行元:Movement Disorder Society of Japan (MDSJ)  

    J-GLOBAL

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  • L-Theanine protects against excess dopamine-induced neurotoxicity in the presence of astrocytes

    Mika Takeshima, Ikuko Miyazaki, Shinki Murakami, Taizo Kita, Masato Asanuma

    JOURNAL OF CLINICAL BIOCHEMISTRY AND NUTRITION   59 ( 2 )   93 - 99   2016年9月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:JOURNAL CLINICAL BIOCHEMISTRY & NUTRITION  

    L-Theanine (gamma-glutamylethylamide), a component of green tea, is considered to have regulatory and neuroprotective roles in the brain. The present study was designed to determine the effect of L-theanine on excess dopamine-induced neurotoxicity in both cell culture and animal experiments. The primary cultured mesencephalic neurons or co-cultures of mesencephalic neurons and striatal astrocytes were pretreated with L-theanine for 72 h, and then treated with excess dopamine for further 24 h. The cell viability of dopamine neurons and levels of glutathione were evaluated. Excess dopamine-induced neurotoxicity was significantly attenuated by 72 h preincubation with L-theanine in neuron-astrocyte co-cultures but not in neuron-rich cultures. Exposure to L-theanine increased the levels of glutathione in both astrocytes and glial conditioned medium. The glial conditioned medium from L-theanine-pretreated striatal astrocytes attenuated dopamine-induced neurotoxicity and quinoprotein formation in mesencephalic neurons. In addition, replacement of L-glutamate with L-theanine in an in vitro cell-free glutathione-synthesis system produced glutathione-like thiol compounds. Furthermore, L-theanine administration (4 mg/kg, p.o.) for 14 days significantly increased glutathione levels in the striatum of mice. The results suggest that L-theanine provides neuroprotection against oxidative stress-induced neuronal damage by humoral molecules released from astrocytes, probably including glutathione.

    DOI: 10.3164/jcbn.16-15

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  • 抗うつ薬ミルタザピンのアストロサイトを標的としたドパミン神経保護(Astrocyte-targeted neuroprotection of antidepressant mirtazapine)

    宮崎 育子, 菊岡 亮, 久保田 菜月, 前田 恵実, 香川 大樹, 守山 雅晃, 粂 明日香, 村上 真樹, 北村 佳久, 浅沼 幹人

    日本神経精神薬理学会年会プログラム・抄録集   46回   232 - 232   2016年7月

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    記述言語:英語   出版者・発行元:(一社)日本神経精神薬理学会  

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  • 筋萎縮性側索硬化症モデルにおける運動障害および運動神経変性に対する8-OH-DPATの抑制効果(8-OH-DPAT ameliorates motor dysfunction and motor neuron degeneration in mouse model of amyotrophic lateral sclerosis)

    浅沼 幹人, 宮崎 育子, 村上 真樹, 鳥越 奈央, 中野 剛志, 菊岡 亮, 北村 佳久, 千堂 年昭

    日本神経精神薬理学会年会プログラム・抄録集   46回   232 - 232   2016年7月

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    記述言語:英語   出版者・発行元:(一社)日本神経精神薬理学会  

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  • パーキンソン病モデルマウスにおけるミルタザピンの神経保護効果に関する検討(Neuroprotective effects of mirtazapine in parkinsonian mice)

    菊岡 亮, 宮崎 育子, 久保田 菜月, 前田 恵実, 香川 大樹, 守山 雅晃, 粂 明日香, 村上 真樹, 北村 佳久, 浅沼 幹人

    日本神経精神薬理学会年会プログラム・抄録集   46回   232 - 232   2016年7月

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    記述言語:英語   出版者・発行元:(一社)日本神経精神薬理学会  

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  • 3-O-Methyldopa inhibits astrocyte-mediated dopaminergic neuroprotective effects of L-DOPA

    Masato Asanuma, Ikuko Miyazaki

    BMC NEUROSCIENCE   17 ( 1 )   2016年7月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:BIOMED CENTRAL LTD  

    Background: We evaluated the effects of 3-O-methyldopa (3-OMD), a metabolite of L-DOPA which is formed by catechol-O-methyltransferase (COMT), on the uptake, metabolism, and neuroprotective effects of L-DOPA in striatal astrocytes. We examined changes in the numbers of dopaminergic neurons after treatment with L-DOPA and 3-OMD or entacapone, a peripheral COMT inhibitor, using primary cultured mesencephalic neurons and striatal astrocytes.
    Results: The number of tyrosine hydroxylase-positive dopaminergic neurons was not affected by L-DOPA treatment in mesencephalic neurons alone. However, the increase in viability of dopaminergic neurons in the presence of astrocytes was further enhanced after methyl-L-DOPA treatment (25 mu M) in mixed cultured mesencephalic neurons and striatal astrocytes. The neuroprotective effect of 25 mu M L-DOPA was almost completely inhibited by simultaneous treatment with 3-OMD (10 or 100 mu M), and was enhanced by concomitant treatment with entacapone (0.3 mu M). The uptake of L-DOPA into and the release of glutathione from striatal astrocytes after L-DOPA treatment (100 mu M) were inhibited by simultaneous exposure to 3-OMD (100 mu M).
    Conclusions: These data suggest that L-DOPA exerts its neuroprotective effect on dopaminergic neurons via astrocytes and that 3-OMD competes with L-DOPA by acting on target molecule(s) (possibly including glutathione) released from astrocytes. Since some amount of entacapone can cross the blood-brain barrier, this reagent may enhance L-DOPA transportation by inhibiting COMT and increase the astrocyte-mediated neuroprotective effects of L-DOPA on dopaminergic neurons.

    DOI: 10.1186/s12868-016-0289-0

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  • In vitro quantitative determination of the concentration of the polymerization agent methyl 2-benzoylbenzoate in intravenous injection solution and the cytotoxic effects of the chemical on normal human peripheral blood mononuclear cells

    Chiaki Tsuboi, Yoichi Kawasaki, Kei Yoshitome, Kenta Yagi, Taro Miura, Satoru Esumi, Ikuko Miyazaki, Masato Asanuma, Yoshihisa Kitamura, Toshiaki Sendo

    ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH   23 ( 10 )   10262 - 10269   2016年5月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:SPRINGER HEIDELBERG  

    In previous studies, we detected the photoinitiators 1-hydroxycyclohexyl phenyl ketone (1-HCHPK) and 2-methyl-4'-(methylthio)-2-morpholinopropiophenone (MTMP) in an intravenous injection solution. Importantly, 1-HCHPK and MTMP have been demonstrated to be cytotoxic to normal human peripheral blood (PB) mononuclear cells (MNC). Cell death (apoptosis) pathways can be classified into two modes, caspase-dependent and -independent pathways. However, it is unclear whether methyl 2-benzoylbenzoate (MBB) induces the caspase-dependent and/or -independent pathway in normal human PBMNC. In the present in vitro study, we examined the levels of MBB in a solution from an intravenous fluid bag and the cytotoxicity of MBB towards normal human PBMNC via the caspase-8-, caspase-9-, or apoptosis-inducing factor (AIF)-mediated apoptosis pathways. We found that extracts from the injection solution had been contaminated with approximately 80 mu M of the photoinitiator MBB. In addition, MBB induced apoptosis in the high concentration range in normal human PBMNC in vitro. Moreover, we found that MBB-induced apoptosis occurs via the caspase-9 pathway, but not the AIF pathway. In conclusion, we suggest that MBB has cytotoxic effects on normal human PBMNC in vitro, which are mediated via the caspase-dependent pathway.

    DOI: 10.1007/s11356-016-6332-y

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  • Changes in Metallothionein Isoform Expression in the Bones of Ovariectomized Rats

    Chiharu Sogawa, Mika Ikegame, Ikuko Miyazaki, Toshiaki Ara, Yasuhiro Imamura, Yuka Okusha, Kazumi Ohyama, Masato Asanuma, Norio Sogawa, Toshio Yamamoto, Ken-ichi Kozaki

    JOURNAL OF HARD TISSUE BIOLOGY   25 ( 1 )   21 - 26   2016年1月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:JOURNAL HARD TISSUE BIOLOGY  

    Metal-binding proteins, metallothioneins (MTs), may play important roles in bone metabolism. However, the contribution of MTs to bone metabolism remains obscure. In the present study, we investigated the expression of MT isoforms in bone cells and mRNA for MT isoforms in the tibiae following ovariectomy (OVX). The results obtained showed that MT-I/II and MT-III were expressed in osteoblasts, osteoclasts, and osteocytes 4 weeks after OVX. Peaks in the mRNA expression ratios (OVX/Sham) of MT-I/II and MT-III changed following OVX. The expression ratio of MT-I/II increased after 1 week, whereas that of MT-III increased 4 weeks after OVX. These results suggest that the contribution of MTs to bone metabolism may depend on the isoforms in the cell types and the stage after OVX.

    DOI: 10.2485/jhtb.25.21

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  • Anti-high mobility group box 1 antibody exerts neuroprotection in a rat model of Parkinson's disease

    Tatsuya Sasaki, Keyue Liu, Takashi Agari, Takao Yasuhara, Jun Morimoto, Mihoko Okazaki, Hayato Takeuchi, Atsuhiko Toyoshima, Susumu Sasada, Aiko Shinko, Akihiko Kondo, Masahiro Kameda, Ikuko Miyazaki, Masato Asanuma, Cesario V. Borlongan, Masahiro Nishibori, Isao Date

    EXPERIMENTAL NEUROLOGY   275 ( 1 )   220 - 231   2016年1月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    The high mobility group box-1 (HMGB1) exists as an architectural nuclear protein in the normal state, but displays an inflammatory cytokine-like activity in the extracellular space under pathological condition. Inflammation in the pathogenesis of Parkinson's disease (PD) has been documented. In this study, we investigated the involvement of HMGB1 in the pathology and the neuroprotective effects of neutralizing anti-HMGB1 monoclonal antibody (mAb) on an animal model of PD. Adult female Sprague-Dawley rats were initially injected with 6-hydroxydopmaine (6-OHDA, 20 mu g/4 mu l) into the right striatum, then anti-HMGB1 mAb (1 mg/kg), or control mAb was intravenously administered immediately, at 6 and 24 h after 6-OHDA injection. The treatment with anti-HMGB1 mAb significantly preserved dopaminergic neurons in substantia nigra pars compacta and dopaminergic terminals inherent in the striatum, and attenuated PD behavioral symptoms compared to the control mAb-treated group. HMGB1 was retained in the nucleus of neurons and astrocytes by inhibiting the proinflammation-induced oxidative stress in the anti-HMGB1 mAb-treated group, whereas HMGB1 translocation was observed in neurons at 1 day and astrocytes at 7 days after 6-OHDA injection in the control mAb-treated group. Anti-HMGB1 mAb inhibited the activation of microglia, disruption of blood-brain-barrier (BBB), and the expression of inflammation cytokines such as IL-1 beta. and IL-6. These results suggested that HMGB1 released from neurons and astrocytes was at least partly involved in the mechanism and pathway of degeneration of dopaminergic neurons induced by 6-0HDA exposure. Intravenous administration of anti-HMGB1 mAb stands as a novel therapy for PD possibly acting through the suppression of neuroinflammation and the attenuation of disruption of BOB associated with the disease. (C) 2015 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.expneurol.2015.11.003

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  • Neuroprotective effects of levetiracetam target xCT in astrocytes in parkinsonian mice

    Ikuko Miyazaki, Shinki Murakami, Nao Torigoe, Yoshihisa Kitamura, Masato Asanuma

    JOURNAL OF NEUROCHEMISTRY   136 ( 1 )   194 - 204   2016年1月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:WILEY-BLACKWELL  

    Astrocytes but not neurons express cystine/glutamate exchange transporter (xCT), which takes up cystine, and consequently supplies the substrate for GSH synthesis in neurons. It is recognized that GSH synthesis in neurons is dependent on the expression of xCT in astrocytes. Previous studies reported that levetiracetam (LEV), an anti-epileptic drug, increased xCT expression invivo. The purpose of this study was to examine neuroprotective effects of LEV in parkinsonian models and demonstrate xCT in astrocytes as a target of neuroprotection against dopaminergic neurodegeneration. We identified striatal astrocytes cultured with LEV showed significant increase in xCT expression and GSH levels. Preincubation of primary cultured mesencephalic dopamine neurons with conditioned media from LEV-treated astrocytes protected against 6-hydroxydopamine (6-OHDA)-induced neurotoxicity. These protective effects were canceled by xCT inhibitor. Furthermore, reduction of nigrostriatal dopaminergic neurons in 6-OHDA-lesioned parkinsonian mice was significantly abrogated by repeated injections of LEV. Treatment with LEV significantly increased the expression of xCT in striatal astrocytes in the hemi-parkinsonian mice. In conclusion, LEV exerts neuroprotective effects against neurodegeneration via up-regulation of xCT and GSH in astrocytes. Thus, xCT in astrocytes could be a potential target in novel neuroprotective approaches to prevent degeneration of dopaminergic neurons.

    DOI: 10.1111/jnc.13405

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  • Serotonin-1A agonist 8-OH-DPAT alleviates motor dysfunction and motor neuron degeneration in a model of amyotrophic lateral sclerosis.

    Miyazaki I, Murakami S, Nakano T, Torigoe N, Kikuoka R, Kitamura Y, Sendo T, Asanuma M

    Ann. Pharmacol. Pharmaceut.   1 ( 1 )   1003 - 1003   2016年

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等  

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  • Serotonin 1A Receptors on Astrocytes as a Potential Target for the Treatment of Parkinson's Disease

    Ikuko Miyazaki, Masato Asanuma

    CURRENT MEDICINAL CHEMISTRY   23 ( 7 )   686 - 700   2016年

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:BENTHAM SCIENCE PUBL LTD  

    Astrocytes are the most abundant neuron-supporting glial cells in the central nervous system. The neuroprotective role of astrocytes has been demonstrated in various neurological disorders such as amyotrophic lateral sclerosis, spinal cord injury, stroke and Parkinson's disease (PD). Astrocyte dysfunction or loss-of-astrocytes increases the susceptibility of neurons to cell death, while astrocyte transplantation in animal studies has therapeutic advantage. We reported recently that stimulation of serotonin 1A (5-HT1A) receptors on astrocytes promoted astrocyte proliferation and upregulated antioxidative molecules to act as a neuroprotectant in parkinsonian mice. PD is a progressive neurodegenerative disease with motor symptoms such as tremor, bradykinesia, rigidity and postural instability, that are based on selective loss of nigrostriatal dopaminergic neurons, and with non-motor symptoms such as orthostatic hypotension and constipation based on peripheral neurodegeneration. Although dopaminergic therapy for managing the motor disability associated with PD is being assessed at present, the main challenge remains the development of neuroprotective or disease-modifying treatments. Therefore, it is desirable to find treatments that can reduce the progression of dopaminergic cell death. In this article, we summarize first the neuroprotective properties of astrocytes targeting certain molecules related to PD. Next, we review neuroprotective effects induced by stimulation of 5-HT1A receptors on astrocytes. The review discusses new promising therapeutic strategies based on neuroprotection against oxidative stress and prevention of dopaminergic neurodegeneration.

    DOI: 10.2174/0929867323666160122115057

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  • Doxorubicin and cyclophosphamide treatment produces anxiety-like behavior and spatial cognition impairment in rats: Possible involvement of hippocampal neurogenesis via brain-derived neurotrophic factor and cyclin D1 regulation

    Yoshihisa Kitamura, Sayo Hattori, Saori Yoneda, Saori Watanabe, Erika Kanemoto, Misaki Sugimoto, Toshiki Kawai, Ayumi Machida, Hirotaka Kanzaki, Ikuko Miyazaki, Masato Asanuma, Toshiaki Sendo

    BEHAVIOURAL BRAIN RESEARCH   292   184 - 193   2015年10月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:ELSEVIER SCIENCE BV  

    Many patients who have received chemotherapy to treat cancer experience depressive- and anxiety-like symptoms or cognitive impairment. However, despite the evidence for this, the underlying mechanisms are still not understood. This study investigated behavioral and biochemical changes upon treatment with doxorubicin and cyclophosphamide, focusing on mental and cognitive systems, as well as neurogenesis in male rats. Doxorubicin (2 mg/kg), cyclophosphamide (50 mg/kg), and the combination of doxorubicin and cyclophosphamide were injected intraperitoneally once per week for 4 weeks. In particular, the co-administration of doxorubicin and cyclophosphamide produced anhedonia-like, anxiety-like, and spatial cognitive impairments in rats. It also reduced both the number of proliferating cells in the subgranular zone of the hippocampal dentate gyrus and their survival. Serum brain-derived neurotrophic factor (BDNF) levels were decreased along with chemotherapy-induced decreases in platelet levels. However, hippocampal BDNF levels and Bdnf mRNA levels were not decreased by this treatment. On the other hand, hippocampal cyclin D1 levels were significantly decreased by chemotherapy. These results suggest that the co-administration of doxorubicin and cyclophosphamide induces psychological and cognitive impairment, in addition to negatively affecting hippocampal neurogenesis, which may be related to hippocampal cyclin D1 levels, but not hippocampal BDNF levels. (C) 2015 Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.bbr.2015.06.007

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  • パーキンソン病モデルマウスにおけるアストロサイトの5‐HT1Aレセプターを標的とした神経保護

    宮崎育子, 宮崎育子, 菊岡亮, 久保田菜月, 前田恵実, 香川大樹, 村上真樹, 村上真樹, 北村佳久, 浅沼幹人, 浅沼幹人

    パーキンソン病・運動障害疾患コングレスプログラム・抄録集   9th   67 - 67   2015年10月

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    記述言語:日本語   出版者・発行元:Movement Disorder Society of Japan (MDSJ)  

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  • ミルタザピンのアストロサイトを標的としたドパミン神経保護効果

    宮崎育子, 菊岡亮, 久保田菜月, 前田恵実, 香川大樹, 村上真樹, 村上真樹, 北村佳久, 浅沼幹人, 浅沼幹人

    日本神経精神薬理学会プログラム・抄録集   45th   185 - 185   2015年9月

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    記述言語:日本語   出版者・発行元:日本生物学的精神医学会・日本神経精神薬理学会  

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  • Long-Term Systemic Exposure to Rotenone Induces Central and Peripheral Pathology of Parkinson's Disease in Mice

    Shinki Murakami, Ikuko Miyazaki, Ko Miyoshi, Masato Asanuma

    NEUROCHEMICAL RESEARCH   40 ( 6 )   1165 - 1178   2015年6月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:SPRINGER/PLENUM PUBLISHERS  

    Parkinson's disease (PD) is a progressive neurodegenerative disease with motor and non-motor symptoms that precede the onset of motor symptoms. Rotenone is often used to induce PD-like pathology in the central nervous system (CNS) and enteric nervous system (ENS). However, there is little or no information on the temporal changes in other neural tissues and the spread of pathology throughout the entire body organs. Here, we recorded the serial immunohistochemical changes in neurons and glial cells of the striatum, substantia nigra (SN), olfactory bulb (OB), thoracic cord (ThC) and ascending colon (AC) induced by 1-, 3- and 6-week administration of rotenone (50 mg/kg/day) infused subcutaneously in C57BL mice using an osmotic pump. Rotenone exposure for 3 or 6 weeks caused neurodegeneration in the striatum, whereas neuronal damage was seen in the SN and OB only after 6 weeks. Moreover, rotenone induced neurodegeneration in the myenteric plexus of AC but not in ThC. Rotenone also activated glial cells before any apparent neurodegeneration in the CNS but not in the ENS. Our results demonstrated that subcutaneous administration of rotenone can cause progressive neurodegeneration in the OB and AC, in addition to the nigrostriatal pathway, and temporal differential glial activation, and that these changes do not spread retrogradely from OB or ENS to nigrostriatal pathway. The results suggested that the different vulnerability of neurons to the neurotoxic effects of rotenone administrated subcutaneously are due to glial activation in these neural tissues.

    DOI: 10.1007/s11064-015-1577-2

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  • ALSモデルマウスにおけるセロトニン1Aアゴニストによる神経保護効果の検討

    中野剛志, 鳥越菜央, 村上真樹, 宮崎育子, 浅沼幹人, 北村佳久, 千堂年昭

    日本薬学会年会要旨集(CD-ROM)   135th ( 3 )   ROMBUNNO.28PB-PM242 - 191   2015年3月

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    記述言語:日本語   出版者・発行元:(公社)日本薬学会  

    J-GLOBAL

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  • ハルミンの薬物依存性ならびに細胞毒性の評価:植物由来幻覚成分の有害作用について. 国際誌

    舩田正彦, 竹林美佳, 宮崎育子, 浅沼幹人, 青尾直也, 和田 清

    精神保健研究   61 ( 28 )   61 - 72   2015年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)  

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  • Visualization of Astrocytic Primary Cilia in the Mouse Brain by Immunofluorescent Analysis Using the Cilia Marker Arl13b

    Kyosuke Kasaharaa, Ko Miyoshi, Shinki Murakami, Ikuko Miyazaki, Masato Asanuma

    ACTA MEDICA OKAYAMA   68 ( 6 )   317 - 322   2014年12月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:OKAYAMA UNIV MED SCHOOL  

    In vertebrates, almost all somatic cells extend a single immotile cilium, referred to as a primary cilium. Increasing evidence suggests that primary cilia serve as cellular antennae in many types of tissues by sensing chemical or mechanical stimuli in the milieu surrounding the cells. In rodents an antibody to adenylyl cyclase 3 (AC3) has been widely used to label the primary cilia of neurons in vivo by immunostaining, whereas the lack of markers for the primary cilia of astrocytes has made it difficult to observe astrocytic primary cilia in vivo. Here, we obtained a visualization of astrocytic primary cilia in the mouse brain. In the somatosensory cortex, a large portion of neurons and astrocytes at postnatal day 10 (P10), and of neurons at P56 had AC3-positive primary cilia, whereas only approx. one-half of the astrocytes in the P56 mice carried primary cilia weakly positive for AC3. In contrast, the majority of astrocytes had ADP-ribosylation factor-like protein 13B (Arl13b)-positive primary cilia in the somatosensory cortex and other brain regions of P56 mice. The lengths of astrocytic primary cilia positive for Arl13b varied among the brain regions. Our data indicate that Arl13b is a noteworthy marker of astrocytic primary cilia in the brain.

    DOI: 10.18926/AMO/53020

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  • Neuroprotective Effects of Metallothionein Against Rotenone-Induced Myenteric Neurodegeneration in Parkinsonian Mice

    Shinki Murakami, Ikuko Miyazaki, Norio Sogawa, Ko Miyoshi, Masato Asanuma

    NEUROTOXICITY RESEARCH   26 ( 3 )   285 - 298   2014年10月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:SPRINGER  

    Parkinson's disease (PD) is a neurodegenerative disease with motor symptoms as well as non-motor symptoms that precede the onset of motor symptoms. Mitochondrial complex I inhibitor, rotenone, has been widely used to reproduce PD pathology in the central nervous system (CNS) and enteric nervous system (ENS). We reported previously that metallothioneins (MTs) released from astrocytes can protect dopaminergic neurons against oxidative stress. The present study examined the changes in MT expression by chronic systemic rotenone administration in the striatum and colonic myenteric plexus of C57BL mice. In addition, we investigated the effects of MT depletion on rotenone-induced neurodegeneration in CNS and ENS using MT-1 and MT-2 knockout (MT KO) mice, or using primary cultured neurons from MT KO mice. In normal C57BL mice, subcutaneous administration of rotenone for 6 weeks caused neurodegeneration, increased MT expression with astrocytes activation in the striatum and myenteric plexus. MT KO mice showed more severe myenteric neuronal damage by rotenone administration after 4 weeks than wild-type mice, accompanied by reduced astroglial activation. In primary cultured mesencephalic neurons from MT KO mice, rotenone exposure induced neurotoxicity in dopaminergic neurons, which was complemented by addition of recombinant protein. The present results suggest that MT seems to provide protection against neurodegeneration in ENS of rotenone-induced PD model mice.

    DOI: 10.1007/s12640-014-9480-1

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  • Methylphenidate improves learning impairments and hyperthermia-induced seizures caused by an Scn1a mutation

    Iori Ohmori, Nozomi Kawakami, Sumei Liu, Haijiao Wang, Ikuko Miyazaki, Masato Asanuma, Hiroyuki Michiue, Hideki Matsui, Tomoji Mashimo, Mamoru Ouchida

    EPILEPSIA   55 ( 10 )   1558 - 1567   2014年10月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:WILEY-BLACKWELL  

    ObjectiveDevelopmental disorders including cognitive deficit, hyperkinetic disorder, and autistic behaviors are frequently comorbid in epileptic patients with SCN1A mutations. However, the mechanisms underlying these developmental disorders are poorly understood and treatments are currently unavailable. Using a rodent model with an Scn1a mutation, we aimed to elucidate the pathophysiologic basis and potential therapeutic treatments for developmental disorders stemming from Scn1a mutations.MethodsWe conducted behavioral analyses on rats with the N1417H-Scn1a mutation. With high-performance liquid chromatography, we measured dopamine and its metabolites in the frontal cortex, striatum, nucleus accumbens, and midbrain. Methylphenidate was administered intraperitoneally to examine its effects on developmental disorder-like behaviors and hyperthermia-induced seizures.ResultsBehavioral studies revealed that Scn1a-mutant rats had repetitive behavior, hyperactivity, anxiety-like behavior, spatial learning impairments, and motor imbalance. Dopamine levels in the striatum and nucleus accumbens in Scn1a-mutant rats were significantly lower than those in wild-type rats. In Scn1a-mutant rats, methylphenidate, by increasing dopamine levels in the synaptic cleft, improved hyperactivity, anxiety-like behavior, and spatial learning impairments. Surprisingly, methylphenidate also strongly suppressed hyperthermia-induced seizures.SignificanceDysfunction of the mesolimbic dopamine reward pathway may contribute to the hyperactivity and learning impairments in Scn1a-mutant rats. Methylphenidate was effective for treating hyperactivity, learning impairments, and hyperthermia-induced seizures. We propose that methylphenidate treatment may ameliorate not only developmental disorders but also epileptic seizures in patients with SCN1A mutations.

    DOI: 10.1111/epi.12750

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  • Striatal Astrocytes Act as a Reservoir for L-DOPA

    Masato Asanuma, Ikuko Miyazaki, Shinki Murakami, Francisco J. Diaz-Corrales, Norio Ogawa

    PLOS ONE   9 ( 9 )   e106362   2014年9月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:PUBLIC LIBRARY SCIENCE  

    L-DOPA is therapeutically efficacious in patients with Parkinson's disease (PD), although dopamine (DA) neurons are severely degenerated. Since cortical astrocytes express neutral amino acid transporter (LAT) and DA transporter (DAT), the uptake and metabolism of L-DOPA and DA in striatal astrocytes may influence their availability in the dopaminergic system of PD. To assess possible L-DOPA-and DA-uptake and metabolic properties of striatal astrocytes, we examined the expression of L-DOPA, DA and DAT in striatal astrocytes of hemi-parkinsonian model rats after repeated L-DOPA administration, and measured the contents of L-DOPA, DA and their metabolite in primary cultured striatal astrocytes after L-DOPA/DA treatment. Repeated injections of L-DOPA induced apparent L-DOPA-and DA-immunoreactivities and marked expression of DAT in reactive astrocytes on the lesioned side of the striatum in hemi-parkinsonian rats. Exposure to DA for 4 h significantly increased the levels of DA and its metabolite DOPAC in cultured striatal astrocytes. L-DOPA was also markedly increased in cultured striatal astrocytes after 4-h L-DOPA exposure, but DA was not detected 4 or 8 h after L-DOPA treatment, despite the expression of aromatic amino acid decarboxylase in astrocytes. Furthermore, the intracellular level of L-DOPA in cultured striatal astrocytes decreased rapidly after removal of extracellular L-DOPA. The results suggest that DA uptaken into striatal astrocytes is rapidly metabolized and that striatal astrocytes act as a reservoir of L-DOPA that govern the uptake or release of L-DOPA depending on extracellular L-DOPA concentration, but are less capable of converting L-DOPA to DA.

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  • Effects of (+)-8-OH-DPAT on the duration of immobility during the forced swim test and hippocampal cell proliferation in ACTH-treated rats

    Ayaka Miyake, Yoshihisa Kitamura, Ikuko Miyazaki, Masato Asanuma, Toshiaki Sendo

    PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR   122   240 - 245   2014年7月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    In the present study, we examined the effect of ACTH on the immobilization of rats in the forced swim test and hippocampal cell proliferation after administration of the 5-HT1A receptor agonist, R-(+)-8-hydroxy-2-di-n-propylamino tetralin ((+)-8-OH-DPAT). Chronic treatment with (+)-8-OH-DPAT (0.01-0.1 mg/kg, s.c.) significantly decreased the duration of immobility in saline- and ACTH-treated rats. Chronic administration of ACTH caused a significant decrease in hippocampal cell proliferation. However, (+)-8-OH-DPAT significantly normalized cell proliferation in ACTH-treated rats. We then investigated the effects of (+)-8-OH-DPAT on the expression of brain-derived neurotrophic factor (BDNF) and cyclin D1 (elements of cyclic adenosine monophosphate response element-binding protein (CREB)-BDNF and Wnt signaling pathways, respectively) in the hippocampus of saline- and ACTH-treated rats. ACTH treatment significantly decreased the expression of cyclin D1, while treatment with (+)-8-OH-DPAT normalized the expression of cyclin D1 in ACTH-treated rats. However, the expression of BDNF did not change in either saline- or ACTH-treated rats. These findings suggest that the antidepressant effects of (+)-8-OH-DPAT in treatment-resistant animals may be attributed to an enhancement of hippocampal cell proliferation, at least in part due to an enhancement of cyclin D1 expression. (C) 2014 Elsevier Inc All rights reserved.

    DOI: 10.1016/j.pbb.2014.04.003

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  • Lack of Dopaminergic Inputs Elongates the Primary Cilia of Striatal Neurons

    Ko Miyoshi, Kyosuke Kasahara, Shinki Murakami, Mika Takeshima, Natsuko Kumamoto, Asako Sato, Ikuko Miyazaki, Shinsuke Matsuzaki, Toshikuni Sasaoka, Taiichi Katayama, Masato Asanuma

    PLOS ONE   9 ( 5 )   e97918   2014年5月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:PUBLIC LIBRARY SCIENCE  

    In the rodent brain, certain G protein-coupled receptors and adenylyl cyclase type 3 are known to localize to the neuronal primary cilium, a primitive sensory organelle protruding singly from almost all neurons. A recent chemical screening study demonstrated that many compounds targeting dopamine receptors regulate the assembly of Chlamydomonas reinhardtii flagella, structures which are analogous to vertebrate cilia. Here we investigated the effects of dopaminergic inputs loss on the architecture of neuronal primary cilia in the rodent striatum, a brain region that receives major dopaminergic projections from the midbrain. We first analyzed the lengths of neuronal cilia in the dorsolateral striatum of hemi-parkinsonian rats with unilateral lesions of the nigrostriatal dopamine pathway. In these rats, the striatal neuronal cilia were significantly longer on the lesioned side than on the non-lesioned side. In mice, the repeated injection of reserpine, a dopamine-depleting agent, elongated neuronal cilia in the striatum. The combined administration of agonists for dopamine receptor type 2 (D2) with reserpine attenuated the elongation of striatal neuronal cilia. Repeated treatment with an antagonist of D2, but not of dopamine receptor type 1 (D1), elongated the striatal neuronal cilia. In addition, D2-null mice displayed longer neuronal cilia in the striatum compared to wild-type controls. Reserpine treatment elongated the striatal neuronal cilia in D1-null mice but not in D2-null mice. Repeated treatment with a D2 agonist suppressed the elongation of striatal neuronal cilia on the lesioned side of hemi-parkinsonian rats. These results suggest that the elongation of striatal neuronal cilia following the lack of dopaminergic inputs is attributable to the absence of dopaminergic transmission via D2 receptors. Our results provide the first evidence that the length of neuronal cilia can be modified by the lack of a neurotransmitter's input.

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  • アストロサイトを介したレベチラセタムのドパミン神経保護効果に関する検討

    宮崎育子, 村上真樹, 鳥越菜央, 北村佳久, 浅沼幹人

    日本薬理学会近畿部会プログラム・要旨集   125th   37   2014年5月

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  • ACTH反復投与ラットにおけるketamineの抗うつ効果に関する検討

    中村紘子, 米田紗緒里, 野白有里子, 宮崎育子, 浅沼幹人, 北村佳久, 千堂年昭

    日本薬学会年会要旨集(CD-ROM)   134th ( 3 )   ROMBUNNO.28PMM-105 - 151   2014年3月

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    記述言語:日本語   出版者・発行元:(公社)日本薬学会  

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  • Protective Effects of Phytochemical Antioxidants Against Neurotoxin-Induced Degeneration of Dopaminergic Neurons

    Taizo Kita, Masato Asanuma, Ikuko Miyazaki, Mika Takeshima

    JOURNAL OF PHARMACOLOGICAL SCIENCES   124 ( 3 )   313 - 319   2014年3月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:JAPANESE PHARMACOLOGICAL SOC  

    The specific toxicity to dopaminergic neurons of psychostimulants and neurotoxins has been extensively studied in vivo and in vitro, and findings have been used to establish animal models of amphetamine psychosis or Parkinson's disease. The multiple mechanisms of neurotoxicity operating in these disorders are known to involve oxidative stress or neuroinflammation, producing the characteristic behavioral and neuropathlogical changes arising from injured dopaminergic neurons and glial cells. A number of studies have shown that glia-targeting antioxidants play important roles in protecting against the neurotoxicity caused by psychostimulants or neurotoxins. Phytochemicals, which are non-nutritive plant chemicals, protect dopaminergic neurons and glial cells from damage caused by psychostimulants or neurotoxins. The objective of this review was to evaluate the involvement of glial cells in dopaminergic neuron specific toxicity and to explore the neuroprotective activity of phytochemicals in terms of anti-inflammatory and antioxidant action.

    DOI: 10.1254/jphs.13R19CP

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  • Effects of Bupropion and Pramipexole on Cell Proliferation in the Hippocampus of Adrenocorticotropic Hormone-Treated Rats

    Yuka Onoue, Keiko Kuwatsuka, Ikuko Miyazaki, Masato Asanuma, Yoshihisa Kitamura, Toshiaki Sendo

    BIOLOGICAL & PHARMACEUTICAL BULLETIN   37 ( 2 )   327 - 330   2014年2月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:PHARMACEUTICAL SOC JAPAN  

    The dopamine reuptake inhibitor bupropion and dopamine D2/3 receptor agonist pramipexole have been clinically proven to improve both depression and treatment-resistant depression. We examined its influence on the duration of immobility during the forced swim test in adrenocorticotropic hormone (ACTH)-treated rats and further analyzed the possible role of the dopamine nerve system in this effect. Bupropion and pramipexole significantly decreased the duration of immobility in normal and ACTH-treated rats. We previously demonstrated that the chronic administration of ACTH caused a significant decrease in hippocampal cell proliferation and neurogenesis. In this study, we used the mitotic marker 5-bromo-2'-deoxyridine to investigate the effects of bupropion and pramipexole on cell proliferation in the subgranular zone of the hippocampal dentate gyms following chronic treatment with ACTH. The ACTH treatment for 14 d decreased adult hippocampal cell proliferation. The chronic administration of bupropion for 14 d blocked the loss of cell proliferation resulting from the chronic treatment with ACTH, whereas pramipexole did not. The administration of bupropion may have treatment-resistant antidepressive properties, which may be partly attributed to the normalization of hippocampal cell proliferation.

    DOI: 10.1248/bpb.b13-00749

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  • Metallothionein deficiency exacerbates diabetic nephropathy in streptozotocin-induced diabetic mice

    Hiromi Tachibana, Daisuke Ogawa, Norio Sogawa, Masato Asanuma, Ikuko Miyazaki, Naoto Terami, Takashi Hatanaka, Chikage Sato Horiguchi, Atsuko Nakatsuka, Jun Eguchi, Jun Wada, Hiroshi Yamada, Kohji Takei, Hirofumi Makino

    AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY   306 ( 1 )   F105 - F115   2014年1月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:AMER PHYSIOLOGICAL SOC  

    Oxidative stress and inflammation play important roles in diabetic complications, including diabetic nephropathy. Metallothionein (MT) is induced in proximal tubular epithelial cells as an antioxidant in the diabetic kidney; however, the role of MT in renal function remains unclear. We therefore investigated whether MT deficiency accelerates diabetic nephropathy through oxidative stress and inflammation. Diabetes was induced by streptozotocin injection in MT-deficient (MT-/-) and MT+/+ mice. Urinary albumin excretion, histological changes, markers for reactive oxygen species (ROS), and kidney inflammation were measured. Murine proximal tubular epithelial (mProx24) cells were used to further elucidate the role of MT under high-glucose conditions. Parameters of diabetic nephropathy and markers of ROS and inflammation were accelerated in diabetic MT-/- mice compared with diabetic MT+/+ mice, despite equivalent levels of hyperglycemia. MT deficiency accelerated interstitial fibrosis and macrophage infiltration into the interstitium in the diabetic kidney. Electron microscopy revealed abnormal mitochondrial morphology in proximal tubular epithelial cells in diabetic MT-/- mice. In vitro studies demonstrated that knockdown of MT by small interfering RNA enhanced mitochondrial ROS generation and inflammation-related gene expression in mProx24 cells cultured under high-glucose conditions. The results of this study suggest that MT may play a key role in protecting the kidney against high glucose-induced ROS and subsequent inflammation in diabetic nephropathy.

    DOI: 10.1152/ajprenal.00034.2013

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  • ALSモデルマウスにおけるセロトニン1Aアゴニストによる神経保護効果の検討

    中野剛志, 鳥越菜央, 村上真樹, 宮崎育子, 浅沼幹人, 北村佳久, 千堂年昭

    日本生物学的精神医学会誌   154   2014年

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  • Neuroprotective effects of levetiracetam in parkinsonian model mice

    Ikuko Miyazaki, Shinki Murakami, Nao Torigoe, Yoshihisa Kitamura, Masato Asanuma

    JOURNAL OF PHARMACOLOGICAL SCIENCES   124   150P - 150P   2014年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:JAPANESE PHARMACOLOGICAL SOC  

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  • 抗がん剤投与ラットにおける精神機能および海馬神経新生に関する検討

    米田紗緒里, 服部紗代, 中村紘子, 宮崎育子, 浅沼幹人, 北村佳久, 千堂年昭

    日本薬学会年会要旨集(CD-ROM)   134th   ROMBUNNO.GS02-7   2014年

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  • Targeting 5-HT1A receptors in astrocytes to protect dopaminergic neurons in parkinsonian models

    Ikuko Miyazaki, Masato Asanuma, Shinki Murakami, Mika Takeshima, Nao Torigoe, Yoshihisa Kitamura, Ko Miyoshi

    Neurobiology of Disease   59 ( 59 )   244 - 256   2013年11月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)  

    Astrocytes are abundant neuron-supporting glial cells that harbor a powerful arsenal of neuroprotective antioxidative molecules and neurotrophic factors. Here we examined whether enrichment with healthy striatal astrocytes can provide neuroprotection against progressive dopaminergic neurodegeneration. Serotonin 1A (5-HT1A) agonist 8-OH-DPAT induced astrocyte proliferation and increased metallothionein-1/-2 (MT-1/-2), antioxidative molecules, in cultured astrocytes and the striatum of mice. Primary cultured mesencephalic dopamine neurons were protected against oxidative stress by preincubation with conditioned media from 8-OH-DPAT-treated astrocytes. These protective effects were canceled by 5-HT1A antagonist or MT-1/-2-specific antibody. Furthermore, reduction of nigrostriatal dopaminergic neurons in 6-hydroxydopamine-lesioned parkinsonian model mice was significantly abrogated by repeated injections of 8-OH-DPAT. Treatment with 8-OH-DPAT markedly increased the expression of MT in striatal astrocytes in the hemi-parkinsonian mice. Our study provides a promising therapeutic strategy of neuroprotection against oxidative stress and progressive dopaminergic neurodegeneration by demonstrating the efficacy of targeting 5-HT1A receptors in astrocytes. © 2013 Elsevier Inc.

    DOI: 10.1016/j.nbd.2013.08.003

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  • 線条体アストロサイトが酸化ストレスに対して発現誘導する因子の網羅的解析

    鳥越 菜央, 宮崎 育子, 村上 真樹, 北村 佳久, 千堂 年昭, 浅沼 幹人

    日本臨床精神神経薬理学会・日本神経精神薬理学会合同年会プログラム・抄録集   23回・43回   250 - 250   2013年10月

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    記述言語:日本語   出版者・発行元:日本臨床精神神経薬理学会・日本神経精神薬理学会  

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  • セロトニン1Aアゴニストによるアストロサイトにおけるメタロチオネイン発現誘導とドパミン神経保護

    宮崎 育子, 村上 真樹, 竹島 美香, 鳥越 菜央, 三好 耕, 北村 佳久, 浅沼 幹人

    日本臨床精神神経薬理学会・日本神経精神薬理学会合同年会プログラム・抄録集   23回・43回   251 - 251   2013年10月

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    記述言語:日本語   出版者・発行元:日本臨床精神神経薬理学会・日本神経精神薬理学会  

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  • Transplantation of Melanocytes Obtained from the Skin Ameliorates Apomorphine-Induced Abnormal Behavior in Rodent Hemi-Parkinsonian Models

    Masato Asanuma, Ikuko Miyazaki, Francisco J. Diaz-Corrales, Youichirou Higashi, Masayoshi Namba, Norio Ogawa

    PLoS ONE   8 ( 6 )   e65983   2013年6月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)  

    Tyrosinase, which catalyzes both the hydroxylation of tyrosine and consequent oxidation of L-DOPA to form melanin in melanocytes, is also expressed in the brain, and oxidizes L-DOPA and dopamine. Replacement of dopamine synthesis by tyrosinase was reported in tyrosine hydroxylase null mice. To examine the potential benefits of autograft cell transplantation for patients with Parkinson's disease, tyrosinase-producing cells including melanocytes, were transplanted into the striatum of hemi-parkinsonian model rats or mice lesioned with 6-hydroxydopamine. Marked improvement in apomorphine-induced rotation was noted at day 40 after intrastriatal melanoma cell transplantation. Transplantation of tyrosinase cDNA-transfected hepatoma cells, which constitutively produce L-DOPA, resulted in marked amelioration of the asymmetric apomorphine-induced rotation in hemi-parkinsonian mice and the effect was present up to 2 months. Moreover, parkinsonian mice transplanted with melanocytes from the back skin of black newborn mice, but not from albino mice, showed marked improvement in the apomorphine-induced rotation behavior up to 3 months after the transplantation. Dopamine-positive signals were seen around the surviving transplants in these experiments. Taken together with previous studies showing dopamine synthesis and metabolism by tyrosinase, these results highlight therapeutic potential of intrastriatal autograft cell transplantation of melanocytes in patients with Parkinson's disease. © 2013 Asanuma et al.

    DOI: 10.1371/journal.pone.0065983

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  • Protective effect of cepharanthin on cisplatin-induced renal toxicity through metallothionein expression

    Norio Sogawa, Kanji Hirai, Chiharu Sogawa, Kazumi Ohyama, Ikuko Miyazaki, Goichi Tsukamoto, Masato Asanuma, Akira Sasaki, Shigeo Kitayama

    Life Sciences   92 ( 12 )   727 - 732   2013年4月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)  

    Aims Cisplatin (CDDP) is a potent anticancer agent, but severe renal toxicity can limit its use. We investigated the protective effect of cepharanthin (CE), a biscoclaurin alkaloid, on the renal toxicity of CDDP. Main methods Mice were given CDDP along with CE. Effects of CE on CDDP toxicity were investigated by assaying markers of renal toxicity together with MT expression, and by histopathological examination of the kidney. MT-null mice were also examined. Key findings CE induced expression of metallothionein (MT). Pre-administration of CE attenuated an increase in blood urea nitrogen (BUN) concentrations after the CDDP injection. A histochemical analysis demonstrated protection against CDDP-induced necrocytosis of kidney tissues by CE. The protective effect of CE did not occur in the MT-null mice. Significance Pretreatment with CE may reduce the renal toxicity of CDDP through expression of MT. © 2013 Elsevier Inc.

    DOI: 10.1016/j.lfs.2013.01.031

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  • アストロサイトとParkinson病治療 国際誌

    浅沼幹人, 宮崎育子

    神経内科   79 ( 2 )   262 - 268   2013年

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  • Neuroprotective effects of serotonin-1a agonist 8-OH-DPAT target astrocytes

    Ikuko Miyazaki, Shinki Murakami, Mika Takeshima, Nao Torigoe, Ko Miyoshi, Yoshihisa Kitamura, Masato Asanuma

    JOURNAL OF PHARMACOLOGICAL SCIENCES   121   138P - 138P   2013年

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  • ラットの行動変化から推察する抗がん剤投与による精神機能変化―ドキソルビシンおよびシクロホスファミド投与による影響―

    北村佳久, 服部紗代, 米田沙緒里, 三宅彩香, 小山敏広, 宮崎育子, 浅沼幹人, 千堂年昭

    日本サイコオンコロジー学会総会プログラム・抄録集   26th   132   2013年

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  • 培養アストログリア細胞における細胞保護効果. 国際誌

    喜多大三, 浅沼幹人, 宮崎育子, 竹島美香

    九州栄養福祉大学研究紀要   ( 10 )   179 - 191   2013年

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  • The mechanisms of electroconvulsive stimuli in BrdU-positive cells of the dentate gyrus in ACTH-treated rats

    Keiko Kuwatsuka, Hiromi Hayashi, Yuka Onoue, Ikuko Miyazaki, Toshihiro Koyama, Masato Asanuma, Yoshihisa Kitamura, Toshiaki Sendo

    Journal of Pharmacological Sciences   122 ( 1 )   34 - 41   2013年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)  

    In clinical studies, electroconvulsive stimuli have been associated with improvements in both depression and treatment-resistant depression. In a previous study, treatment with adrenocorticotropic hormone (ACTH) for 14 days decreased adult hippocampal cell proliferation. Furthermore, electroconvulsive stimuli significantly decreased the duration of immobility following repeated administration of ACTH for 14 days in rats. The present study was undertaken to further characterize the mechanism of treatment-resistant antidepressant effects of electroconvulsive stimuli by measuring cell proliferation, brain-derived neurotrophic factor (BDNF) levels, and phosphorylated and total cyclic adenosine monophosphate (cAMP) response element-binding protein (pCREB/CREB) levels in the hippocampus of ACTH-treated rats. Electroconvulsive stimuli increased cell proliferation in both saline-treated and ACTH-treated rats. Mature-BDNF protein levels showed a tendency to decrease in ACTH-treated rats. Electroconvulsive stimuli treatment increased mature-BDNF protein levels in the hippocampus of both saline-treated and ACTH-treated rats. Furthermore, electroconvulsive stimuli increased phospho-Ser133-CREB (pCREB) levels and the ratio of pCREB/CREB in both saline-treated and ACTH-treated rats. These findings suggest that the treatment-resistant antidepressant effects of electroconvulsive stimuli may be attributed, at least in part, to an enhancement of hippocampal cell proliferation. © The Japanese Pharmacological Society.

    DOI: 10.1254/jphs.13015FP

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  • Effect of the 5-HT1A receptor function on antidepressive effect and neurogenesis in ACTH treated rats 査読

    Miyake Ayaka, Kitamura Yoshihisa, Hattori Sayo, Koyama Toshihiro, Miyazaki Ikuko, Asanuma Masato, Sendo Toshiaki

    JOURNAL OF PHARMACOLOGICAL SCIENCES   121   144P   2013年

  • Influence of doxorubicin and cyclophosphamide on psychological behavior in rats 査読

    Kitamura Yoshihisa, Hattori Sayo, Miyake Ayaka, Koyama Toshihiro, Miyazaki Ikuko, Asanuma Masato, Sendo Toshiaki

    JOURNAL OF PHARMACOLOGICAL SCIENCES   121   143P   2013年

  • Centrosomal aggregates and Golgi fragmentation disrupt vesicular trafficking of DAT

    Francisco J. Diaz-Corrales, Ikuko Miyazaki, Masato Asanuma, Diego Ruano, Rosa M. Rios

    NEUROBIOLOGY OF AGING   33 ( 10 )   2462 - 2477   2012年10月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:ELSEVIER SCIENCE INC  

    Lewy bodies containing the centrosomal protein gamma-tubulin and fragmentation of Golgi apparatus (GA) have been described in nigral neurons of Parkinson's disease (PD) patients. However, the relevance of these features in PD pathophysiology remains unknown. We analyzed the impact of proteasome inhibition in the formation of gamma-tubulin-containing aggregates as well as on GA structure. SH-SY5Y cells were treated with the proteasome inhibitor Z-Leu-Leu-Leu-al (MG132) to induce centrosomal-protein aggregates. Then, microtubules (MTs) and Golgi dynamics, as well as the vesicular transport of dopamine transporter (DAT) were evaluated both in vitro and in living cells. MG132 treatment induced gamma-tubulin aggregates which altered microtubule nucleation. MG132-treated cells containing gamma-tubulin aggregates showed fragmentation of GA and perturbation of the trans-Golgi network. Under these conditions, the DAT accumulated at the centrosomal-Golgi region indicating that the vesicular transport of DAT was disrupted. Thus, centrosomal aggregates and fragmentation of GA are 2 closely related processes that could result in the disruption of the vesicular transport of DAT toward the plasma membrane in a model of dopaminergic neuronal degeneration. (C) 2012 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.neurobiolaging.2011.11.014

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  • Cyclooxygenase-Independent Neuroprotective Effects of Aspirin Against Dopamine Quinone-Induced Neurotoxicity

    Masato Asanuma, Ikuko Miyazaki, Yuri Kikkawa, Naotaka Kimoto, Mika Takeshima, Shinki Murakami, Ko Miyoshi

    NEUROCHEMICAL RESEARCH   37 ( 9 )   1944 - 1951   2012年9月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:SPRINGER/PLENUM PUBLISHERS  

    Prostaglandin H synthase exerts not only cyclooxygenase activity but also peroxidase activity. The latter activity of the enzyme is thought to couple with oxidation of dopamine to dopamine quinone. Therefore, it has been proposed that cyclooxygenase inhibitors could suppress dopamine quinone formation. In the present study, we examined effects of various cyclooxygenase inhibitors against excess methyl L-3,4-dihydroxyphenylalanine (L-DOPA)-induced quinoprotein (protein-bound quinone) formation and neurotoxicity using dopaminergic CATH.a cells. The treatment with aspirin inhibited excess methyl L-DOPA-induced quinoprotein formation and cell death. However, acetaminophen did not show protective effects, and indomethacin and meloxicam rather aggravated these methyl L-DOPA-induced changes. Aspirin and indomethacin did not affect the level of glutathione that exerts quenching dopamine quinone in dopaminergic cells. In contrast with inhibiting effects of higher dose in the previous reports, relatively lower dose of aspirin that affected methyl L-DOPA-induced quinoprotein formation and cell death failed to prevent cyclooxygenase-induced dopamine chrome generation in cell-free system. Furthermore, aspirin but not acetaminophen or meloxicam showed direct dopamine quinone-scavenging effects in dopamine-semiquinone generating systems. The present results suggest that cyclooxygenase shows little contribution to dopamine oxidation in dopaminergic cells and that protective effects of aspirin against methyl L-DOPA-induced dopamine quinone neurotoxicity are based on its cyclooxygenase-independent property.

    DOI: 10.1007/s11064-012-0813-2

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  • EFFLUENT FREE RADICALS ARE ASSOCIATED WITH RESIDUAL RENAL FUNCTION AND PREDICT TECHNIQUE FAILURE IN PERITONEAL DIALYSIS PATIENTS

    Hiroshi Morinaga, Hitoshi Sugiyama, Tatsuyuki Inoue, Keiichi Takiue, Yoko Kikumoto, Masashi Kitagawa, Shigeru Akagi, Kazushi Nakao, Yohei Maeshima, Ikuko Miyazaki, Masato Asanuma, Makoto Hiramatsu, Hirofumi Makino

    PERITONEAL DIALYSIS INTERNATIONAL   32 ( 4 )   453 - 461   2012年7月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:MULTIMED INC  

    Objective: Residual renal function (RRF) is associated with low oxidative stress in peritoneal dialysis (PD). In the present study, we investigated the relationship between the impact of oxidative stress on RRF and patient outcomes during PD.
    Methods: Levels of free radicals (FRs) in effluent from the overnight dwell in 45 outpatients were determined by electron spin resonance spectrometry. The FR levels, clinical parameters, and the level of 8-hydroxy-2'-deoxyguanosine were evaluated at study start. The effects of effluent FR level on technique and patient survival were analyzed in a prospective cohort followed for 24 months.
    Results: Levels of effluent FRs showed significant negative correlations with daily urine volume and residual renal Kt/V, and positive correlations with plasma beta(2)-microglobulin and effluent 8-hydroxy-2'-deoxyguanosine. A highly significant difference in technique survival (p &lt; 0.05), but not patient survival, was observed for patients grouped by effluent FR quartile. The effluent FR level was independently associated with technique failure after adjusting for patient age, history of cardiovascular disease, and presence of diabetes mellitus (p &lt; 0.001). The level of effluent FRs was associated with death-censored technique failure in both univariate (p &lt; 0.001) and multivariate (p &lt; 0.01) hazard models. Compared with patients remaining on PD, those withdrawn from the modality had significantly higher levels of effluent FRs (p &lt; 0.005).
    Conclusions: Elevated effluent FRs are associated with RRF and technique failure in stable PD patients. These findings highlight the importance of oxidative stress as an unfavorable prognostic factor in PD and emphasize that steps should be taken to minimize oxidative stress in these patients. Perit Dial Int 2012; 32(4): 453-461

    DOI: 10.3747/pdi.2011.00032

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  • Investigation on the Mechanisms for the Suppression of Cell Proliferation in the Dentate Gyrus of the Hippocampus in ACTH Treated Rats

    Hiromi Hayashi, Maho Doi, Yuka Onoue, Keiko Kuwatsuka, Ayaka Miyake, Toshihiro Koyama, Kazuaki Shinomiya, Ikuko Miyazaki, Masato Aasanuma, Yoshihisa Kitamura

    YAKUGAKU ZASSHI-JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN   132 ( 2 )   173 - 178   2012年2月

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    記述言語:日本語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:PHARMACEUTICAL SOC JAPAN  

    We previously reported that adrenocorticotropic hormone (ACTH) -treated rats serve as a valuable animal model for tricyclic antidepressant-resistant depressive conditions. The present study was undertaken to investigate the changes in neurogenesis in the hippocampus of ACTH-treated rats. Chronic treatment of ACTH decreased the number of bromodeoxyuridine-labeled cells in the dentate gyrus, and the coadministration of imipramine and lithium, and electroconvulsive stimuli recovered these reductions. Furthermore, chronic ACTH treatment also decreased the expression of brain-derived neurotrophic factor, and the coadministration of imipramine and lithium, and electroconvulsive stimuli recovered these reductions. These results suggest that antidepressant-resistant depression is caused by the suppression of neurogenesis, and the coadministration of imipramine and lithium, and electroconvulsive stimuli exert an antidepressant-like effect by recovering proliferative signals and neurogenesis.

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  • ACTH反復投与ラットにおける海馬細胞新生の減少及びそのメカニズムに関する検討. 国際誌

    林 宏美, 土居真穂, 尾上由華, 鍬塚圭子, 三宅彩香, 小山敏広, 四宮一昭, 宮崎育子, 浅沼幹人, 北村佳久

    薬学雑誌   173 - 178   2012年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)  

    DOI: 10.1248/yakushi.132.173

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  • Neuroprotective effects of serotonin-1a agonist 8-OH-DPAT in parkinsonian mice

    Ikuko Miyazaki, Shinki Murakami, Mika Takeshima, Masato Asanuma

    JOURNAL OF PHARMACOLOGICAL SCIENCES   118   111P - 111P   2012年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:JAPANESE PHARMACOLOGICAL SOC  

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  • Chronic rotenone exposure affects enteric glial cells

    Shinki Murakami, Ikuko Miyazaki, Masato Asanuma

    JOURNAL OF PHARMACOLOGICAL SCIENCES   118   188P - 188P   2012年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:JAPANESE PHARMACOLOGICAL SOC  

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  • テアニンの中枢作用に関する文献的考察. 国際誌

    喜多大三, 浅沼幹人, 宮崎育子, 竹島美香

    九州栄養福祉大学研究紀要   45 - 58   2012年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)  

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  • Protective effects of baicalein against excess L-DOPA-induced dopamine quinone neurotoxicity

    Mika Takeshima, Maiko Murata, Natsuho Urasoe, Shinki Murakami, Ikuko Miyazaki, Masato Asanuma, Taizo Kita

    NEUROLOGICAL RESEARCH   33 ( 10 )   1050 - 1056   2011年12月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:MANEY PUBLISHING  

    Objectives: Baicalein, a flavonoid derived from the root of Scutelaria baicalensis Georgi, possesses antioxidative properties including reactive oxygen species scavenging and lipid peroxidation inhibiting activities. The present study was undertaken to investigate the neuroprotective effect of baicalein against dopamine (DA) neurotoxicity induced by exposure to a synthetic DA precursor, L-3,4-dihydroxyphenylalanine (L-DOPA), in cultured dopaminergic CATH. a cells.
    Methods and results: Exposure to L-DOPA for 24 hours reduced the number of viable cells and enhanced protein-bound quinone (quinoprotein) formation in the cell. Both effects were prevented by simultaneous treatment with baicalein. In addition, baicalein prevented the formation of DA semiquinone radicals from DA in an in vitro cell-free system. Long-term baicalein treatment for 96 hours also protected against excess L-DOPA-induced cell death, and also increased glutathione (GSH) levels in CATH. a cells.
    Discussion: Our results indicate that baicalein has neuroprotective properties against excess L-DOPA-induced DA neurotoxicity through the suppression of DA quinone formation. Furthermore, the long-term treatment of baicalein upregulates intracellular GSH contents, which may also exert neuroprotective effects against oxidative stress-induced neuronal damage.

    DOI: 10.1179/1743132811Y.0000000032

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  • Factors That Influence Primary Cilium Length

    Ko Miyoshi, Kyosuke Kasahara, Ikuko Miyazaki, Masato Asanuma

    ACTA MEDICA OKAYAMA   65 ( 5 )   279 - 285   2011年10月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:OKAYAMA UNIV MED SCHOOL  

    Almost all mammalian cells carry one primary cilium that functions as a biosensor for chemical and mechanical stimuli. Genetic damages that compromise cilia formation or function cause a spectrum of disorders referred to as ciliapathies. Recent studies have demonstrated that some pharmacological agents and extracellular environmental changes can alter primary cilium length. Renal injury is a well-known example of an environmental insult that triggers cilia length modification. Lithium treatment causes primary cilia to extend in several cell types including neuronal cells; this phenomenon is likely independent of glycogen synthase kinase-3 beta inhibition. In renal epithelial cell lines, deflection of the primary cilia by fluid shear shortens them by reducing the intracellular cyclic AMP level, leading to a subsequent decrease in mechanosensitivity to fluid shear. Primary cilium length is also influenced by the dynamics of actin filaments and microtubules through the levels of soluble tubulin in the cytosol available for primary cilia extension. Thus, mammalian cells can adapt to the extracellular environment by modulating the primary cilium length, and this feedback system utilizing primary cilia might exist throughout the mammalian body. Further investigation is required concerning the precise molecular mechanisms underlying the control of primary cilium length in response to environmental factors.

    DOI: 10.18926/AMO/47009

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  • ACTH反復投与ラットにおける海馬細胞新生の減少およびそのメカニズムに関する検討

    林宏美, 土居真穂, 尾上由華, 鍬塚圭子, 三宅彩香, 小山敏広, 四宮一昭, 宮崎育子, 浅沼幹人, 北村佳久

    日本薬学会年会要旨集   131st ( 1 )   257   2011年3月

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    記述言語:日本語  

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  • Astrocyte-Derived Metallothionein Protects Dopaminergic Neurons from Dopamine Quinone Toxicity

    Ikuko Miyazaki, Masato Asanuma, Yuri Kikkawa, Mika Takeshima, Shinki Murakami, Ko Miyoshi, Norio Sogawa, Taizo Kita

    GLIA   59 ( 3 )   435 - 451   2011年3月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:WILEY-LISS  

    Our previous studies demonstrated the involvement of quinone formation in dopaminergic neuron dysfunction in the L-DOPA-treated parkinsonian model and in methamphetamine (METH) neurotoxicity. We further reported that the cysteine-rich metal-binding metallothionein (MT) family of proteins protects dopaminergic neurons against dopamine (DA) quinone neurotoxicity by its quinone-quenching property. The aim of this study was to examine MT induction in astrocytes in response to excess DA and the potential neuroprotective effects of astrocyte-derived MTs against DA quinone toxicity. DA exposure significantly upregulated MT-1/-2 in cultured striatal astrocytes, but not in mesencephalic neurons. This DA-induced MT upregulation in astrocytes was blocked by treatment with a DA-transporter (DAT) inhibitor, but not by DA-receptor antagonists. Expression of nuclear factor erythroid 2-related factor (Nrf2) and its binding activity to antioxidant response element of MT-1 gene were significantly increased in the astrocytes after DA exposure. Nuclear translocation of Nrf2 was suppressed by the DAT inhibitor. Quinone formation and reduction of mesencephalic DA neurons after DA exposure were ameliorated by preincubation with conditioned media from DA-treated astrocytes. These protective effects were abrogated by MT-1/-2-specific antibody. Adding exogenous MT-1 to glial conditioned media also showed similar neuroprotective effects. Furthermore, MT-1/-2 expression was markedly elevated specifically in reactive astrocytes in the striatum of L-DOPA-treated hemi-parkinsonian mice or METH-injected mice. These results suggested that excess DA taken up by astrocytes via DAT upregulates MT-1/-2 expression specifically in astrocytes, and that MTs or related molecules secreted specifically by astrocytes protect dopaminergic neurons from damage through quinone quenching and/or scavenging of free radicals. (C)2010 Wiley-Liss, Inc.

    DOI: 10.1002/glia.21112

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  • A Novel Hypothesized Clinical Implication of Zonisamide for Autism Reply

    Masato Asanuma, Ikuko Miyazaki

    ANNALS OF NEUROLOGY   69 ( 2 )   426 - 427   2011年2月

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    記述言語:英語   掲載種別:速報,短報,研究ノート等(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    DOI: 10.1002/ana.22347

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  • Chronic Treatment with Imipramine and Lithium Increases Cell Proliferation in the Hippocampus in Adrenocorticotropic Hormone-Treated Rats

    Yoshihisa Kitamura, Maho Doi, Keiko Kuwatsuka, Yuka Onoue, Ikuko Miyazaki, Kazuaki Shinomiya, Toshihiro Koyama, Toshiaki Sendo, Hiromu Kawasaki, Masato Asanuma, Yutaka Gomita

    BIOLOGICAL & PHARMACEUTICAL BULLETIN   34 ( 1 )   77 - 81   2011年1月

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    記述言語:英語   掲載種別:速報,短報,研究ノート等(学術雑誌)   出版者・発行元:PHARMACEUTICAL SOC JAPAN  

    Adult hippocampal neurogenesis is reported to change in animal models of depression and antidepressants. We have used the mitotic marker 5-bromo-2'-deoxyyridine to address the effects of imipramine and lithium on cell proliferation and survival following chronic treatment with adrenocorticotropic hormone (ACTH) in the subgranular zone of the hippocampal dentate gyrus. ACTH treatment for 14d decreased adult hippocampal cell proliferation and survival. Coadministration of imipramine and lithium for 14d blocked the loss of cell proliferation but not cell survival resulting from the chronic treatment with ACTH. The coadministration of imipramine and lithium may have treatment-resistant antidepressive properties, which may be attributed, in part, to a normalization of hippocampal cell proliferation.

    DOI: 10.1248/bpb.34.77

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  • High glucose increases metallothionein expression in renal proximal tubular epithelial cells.

    Ogawa D, Asanuma M, Miyazaki, I, Tachibana H, Wada J, Sogawa N, Sugaya T, Kitamura S, Maeshima Y, Shikata K, Makino F

    Exp Diabetes Res   2011   1 - 8   2011年

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    記述言語:英語   掲載種別:速報,短報,研究ノート等(学術雑誌)  

    DOI: 10.1155/2011/534872

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  • Dopamine receptors localize to the neuronal primary cilium, a non-synaptic neurotransmission device

    Ko Miyoshi, Kyosuke Kasahara, Shinki Murakami, Ikuko Miyazaki, Masato Asanuma

    NEUROSCIENCE RESEARCH   71   E87 - E87   2011年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:ELSEVIER IRELAND LTD  

    DOI: 10.1016/j.neures.2011.07.372

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  • Effects of imipramine and lithium on the suppression of cell proliferation in the dentate gyrus of the hippocampus in ACTH treated rats

    Hiromi Hayashi, Maho Doi, Yuka Onoue, Keiko Kuwatsuka, Ayaka Miyake, Toshihiro Koyama, Kazuaki Shinomiya, Ikuko Miyazaki, Masato Asanuma, Yoshihisa Kitamura

    JOURNAL OF PHARMACOLOGICAL SCIENCES   115   251P - 251P   2011年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:JAPANESE PHARMACOLOGICAL SOC  

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  • Effects of chronic rotenone exposure on enteric neuronal or glial cells in vivo

    Shinki Murakami, Ikuko Miyazaki, Mika Takeshima, Ko Miyoshi, Masato Asanuma

    NEUROSCIENCE RESEARCH   71   E190 - E190   2011年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:ELSEVIER IRELAND LTD  

    DOI: 10.1016/j.neures.2011.07.821

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  • Effects of rotenone exposure on primary cultured enteric neuronal or glial cells

    Ikuko Miyazaki, Shinki Murakami, Mika Takeshima, Ko Miyoshi, Masato Asanuma

    NEUROSCIENCE RESEARCH   71   E190 - E190   2011年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:ELSEVIER IRELAND LTD  

    DOI: 10.1016/j.neures.2011.07.820

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  • L-テアニンのグリア細胞に対する保護作用に関する研究─アストロサイトにおけるL-テアニンによる抗酸化保護作用の賦活─ 国際誌

    喜多大三, 浅沼幹人, 宮崎育子, 竹島美香

    九州栄養福祉大学研究紀要   8   43 - 53   2011年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)  

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  • パーキンソン病とアストロサイト─新たな神経保護療法の標的 国際誌

    浅沼幹人, 宮崎育子

    Clinical Neuroscience   29   1295 - 1297   2011年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)  

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  • Effects of Imipramine and Lithium on the Suppression of Cell Proliferation in the Dentate Gyrus of the Hippocampus in Adrenocorticotropic Hormone-treated Rats

    Maho Doi, Ikuko Miyazaki, Tomoko Nagamachi, Kazuaki Shinomiya, Hisashi Matsunaga, Toshiaki Sendo, Hiromu Kawasaki, Masato Asanuma, Yutaka Gomita, Yoshihisa Kitamura

    ACTA MEDICA OKAYAMA   64 ( 4 )   219 - 223   2010年8月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:OKAYAMA UNIV MED SCHOOL  

    We examined the influence of chronic adrenocorticotropic hormone (ACTH) treatment on the number of Ki-67-positive cells in the dentate gyrus of the hippocampus in rats. ACTH treatment for 14 days decreased the number of such cells. The administration of imipramine or lithium alone for 14 days had no effect in saline-treated rats. The effect of ACTH was blocked by the administration of imipramine. Furthermore, the coadministration of imipramine and lithium for 14 days significantly increased the number of Ki-67-positive cells in both the saline and ACTH-treated rats. The coadministration of imipramine and lithium normalized the cell proliferation in the dentate gyrus of the hippocampus in rats treated with ACTH.

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  • Neuroprotective Effects of Zonisamide Target Astrocyte

    Masato Asanuma, Ikuko Miyazaki, Francisco J. Diaz-Corrales, Naotaka Kimoto, Yuri Kikkawa, Mika Takeshima, Ko Miyoshi, Miho Murata

    ANNALS OF NEUROLOGY   67 ( 2 )   239 - 249   2010年2月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:WILEY-LISS  

    Objective: Recent double-blind, controlled trials in Japan showed that the antiepileptic agent zonisamide (ZNS)improves the cardinal symptoms of Parkinson&apos;s disease. Glutathione (GSH) exerts antioxidative activity through quenching reactive oxygen species and dopamine quinone. GSH depletion within dopaminergic neurons impairs mitochondrial complex I activity, followed by age-dependent nigrostriatal neurodegeneration. This study examined changes in GSH and GSH synthesis-related molecules, and the neuroprotective effects of ZNS on dopaminergic neurodegeneration using 6-hydroxydopamine-injected hemiparkinsonian mice brain and cultured neurons or astrocytes.
    Methods and Results: ZNS increased both the cell number and GSH levels in astroglial C6 cells, but not in dopaminergic neuronal CATH.a cells. Repeated injections of ZNS (30mg/kg intraperitoneally) for 14 days also significantly increased GSH levels and S100 beta-positive astrocytes in mouse basal ganglia. Repeated ZNS injections (30mg/kg) for 7 days in the hemiparkinsonian mice increased the expression of cystine/glutamate exchange transporter xCT in activated astrocytes, which supply cysteine to neurons for GSH synthesis. Treatment of these mice with ZNS also increased GSH levels and completely suppressed striatal levodopa-induced quinone formation. Reduction of nigrostriatal dopamine neurons in the lesioned side of hemiparkinsonian mice was significantly abrogated by repeated injections of ZNS with or without adjunctive levodopa starting 3 weeks after 6-hydroxydopamine lesioning.
    Interpretation: These results provide new pharmacological evidence for the effects of ZNS. ZNS markedly increased GSH levels by enhancing the astroglial cystine transport system and/or astroglial proliferation via S100 beta production or secretion. ZNS acts as a neuroprotectant against oxidative stress and progressive dopaminergic neurodegeneration. ANN NEUROL 2010;67:239-249

    DOI: 10.1002/ana.21885

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  • Dopamine-specific metallothionein induction in reactive astrocytes through dopamine transporter

    Ikuko Miyazaki, Yuri Kikkawa, Mika Takeshima, Masato Asanuma

    JOURNAL OF PHARMACOLOGICAL SCIENCES   112   91P - 91P   2010年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:JAPANESE PHARMACOLOGICAL SOC  

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  • L-theanine up-regulates glutathione levels in astrocytes and protects excess dopamine-induced neurotoxicity

    Mika Takeshima, Ikuko Miyazaki, Yuri Kikkawa, Taizo Kita, Masato Asanuma

    JOURNAL OF PHARMACOLOGICAL SCIENCES   112   54P - 54P   2010年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:JAPANESE PHARMACOLOGICAL SOC  

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  • Effects of docosahexaenoic acid on methamphetamine-induced neurotoxicity in cultured dopaminergic neuronal cells

    Maiko Murata, Natsuho Urasoe, Ikuko Miyazaki, Masato Asanuma, Taizo Kita

    JOURNAL OF PHARMACOLOGICAL SCIENCES   112   139P - 139P   2010年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:JAPANESE PHARMACOLOGICAL SOC  

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  • Lithium elongates neuronal primary cilia

    Ko Miyoshi, Kyosuke Kasahara, Ikuko Miyazaki, Masato Asanuma

    NEUROSCIENCE RESEARCH   68   E84 - E84   2010年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:ELSEVIER IRELAND LTD  

    DOI: 10.1016/j.neures.2010.07.138

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  • Astrocytes protect dopaminergic neurons from dopamine quinone toxicity

    Ikuko Miyazaki, Yuri Kikkawa, Mika Takeshima, Ko Miyoshi, Taizo Kita, Masato Asanuma

    NEUROSCIENCE RESEARCH   68   E347 - E347   2010年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:ELSEVIER IRELAND LTD  

    DOI: 10.1016/j.neures.2010.07.1537

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  • Involvement of nicotinic acetylcholine receptor on the conditioned place aversion behavior and c-Fos expression induced by naloxone in single-dose morphine-treated rats 査読

    Ikuta Yuichi, Ishida Shigeru, Miyazaki Ikuko, Asanuma Masato, Araki Hiroaki, Matsunaga Hisashi, Kitamura Yoshihisa, Sendo Toshiaki

    JOURNAL OF PHARMACOLOGICAL SCIENCES   112   187P   2010年

  • Effects of cell proliferation and astroglial activity by the chronic treatment of ACTH in the hippocampal dentate gyrus of adult rats 査読

    Doi Maho, Nagamachi Tomoko, Egawa Maki, Miyazaki Ikuko, Kawasaki Hiromu, Sendo Toshiaki, Asanuma Masato, Kitamura Yoshihisa

    JOURNAL OF PHARMACOLOGICAL SCIENCES   112   178P   2010年

  • Pericentrin, a centrosomal protein related to microcephalic primordial dwarfism, is required for olfactory cilia assembly in mice

    Ko Miyoshi, Kyosuke Kasahara, Ikuko Miyazaki, Shoko Shimizu, Manabu Taniguchi, Shinsuke Matsuzaki, Masaya Tohyama, Masato Asanuma

    FASEB JOURNAL   23 ( 10 )   3289 - 3297   2009年10月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:FEDERATION AMER SOC EXP BIOL  

    The Drosophila pericentrin-like protein has been shown to be essential for the formation of the sensory cilia of chemosensory and mechanosensory neurons by mutant analysis in flies, while the in vivo function of pericentrin, a well-studied mammalian centrosomal protein related to microcephalic primordial dwarfism, has been unclear. To determine whether pericentrin is required for ciliogenesis in mammals, we generated and analyzed mice with a hypomorphic mutation of Pcnt encoding the mouse pericentrin. Immunofluorescence analysis demonstrated that olfactory cilia of chemosensory neurons in the nasal olfactory epithelium were malformed in the homozygous mutant mice. On the other hand, the assembly of motile and primary cilia of non-neuronal epithelial cells and the formation of sperm flagella were not affected in the Pcnt-mutant mice. The defective assembly of olfactory cilia in the mutant was apparent from birth. The mutant animals displayed reduced olfactory performance in agreement with the compromised assembly of olfactory cilia. Our findings suggest that pericentrin is essential for the assembly of chemosensory cilia of olfactory receptor neurons, but it is not globally required for cilia formation in mammals.-Miyoshi, K., Kasahara, K., Miyazaki, I., Shimizu, S., Taniguchi, M., Matsuzaki, S., Tohyama, M., Asanuma, M. Pericentrin, a centrosomal protein related to microcephalic primordial dwarfism, is required for olfactory cilia assembly in mice. FASEB J. 23, 3289-3297 ( 2009). www.fasebj.org

    DOI: 10.1096/fj.08-124420

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  • Lithium treatment elongates primary cilia in the mouse brain and in cultured cells

    Ko Miyoshi, Kyosuke Kasahara, Ikuko Miyazaki, Masato Asanuma

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   388 ( 4 )   757 - 762   2009年10月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    The molecular mechanisms underlying the therapeutic effects of lithium, a first-line antimanic mood stabilizer, have not yet been fully elucidated. Treatment of the algae Chlamydomonas reinhardtii with lithium has been shown to induce elongation of their flagella, which are analogous structures to vertebrate cilia. In the mouse brain, adenylyl cyclase 3 (AC3) and certain neuropeptide receptors colocalize to the primary cilium of neuronal cells, suggesting a chemosensory function for the primary cilium in the nervous system. Here we show that lithium treatment elongates primary cilia in the mouse brain and in cultured cells. Brain sections from mice chronically fed with Li(2)CO(3) were subjected to immunofluorescence study. Primary cilia carrying both AC3 and the receptor for melanin-concentrating hormone (MCH) were elongated in the dorsal striatum and nucleus accumbens of lithium-fed mice, as compared to those of control animals. Moreover, lithium-treated NIH3T3 cells and cultured striatal neurons exhibited elongation of the primary cilia. The present results provide initial evidence that a psychotropic agent can affect ciliary length in the central nervous system, and furthermore suggest that lithium exerts its therapeutic effects via the upregulation of cilia-mediated MCH sensing. These findings thus contribute novel insights into the pathophysiology of bipolar mood disorder and other psychiatric diseases. (C) 2009 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.bbrc.2009.08.099

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  • REDUCTION OF PPAR-gamma IN METHAMPHETAMINE-INDUCED NEUROTOXICITY AND PROTECTIVE EFFECTS OF INTERFERON-gamma

    M. Asanuma, Miyazaki, I, Y. Kikkawa, M. Takeshima, K. Miyoshi, T. Kita

    JOURNAL OF NEUROCHEMISTRY   110   49 - 49   2009年9月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:WILEY-BLACKWELL PUBLISHING, INC  

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  • メタンフェタミン神経毒性に対するインターフェロンγおよびPPARγアゴニストの保護効果(Protective effects of interferon-γ or peroxisome proliferator-activated receptor-γ agonist against methamphetamine-induced neurotoxicity)

    浅沼 幹人, 宮崎 育子, 福岡 早紀, 穂積 宏彰, 辻 武史, 北村 佳久, 千堂 年昭, 喜多 大三

    神経化学   48 ( 2-3 )   214 - 214   2009年6月

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    記述言語:英語   出版者・発行元:日本神経化学会  

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  • Reduction of Nuclear Peroxisome Proliferator-Activated Receptor gamma Expression in Methamphetamine-Induced Neurotoxicity and Neuroprotective Effects of Ibuprofen

    Takeshi Tsuji, Masato Asanuma, Ikuko Miyazaki, Ko Miyoshi, Norio Ogawa

    NEUROCHEMICAL RESEARCH   34 ( 4 )   764 - 774   2009年4月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:SPRINGER/PLENUM PUBLISHERS  

    We examined changes in nuclear peroxisome proliferator-activated receptor gamma (PPAR gamma) in the striatum in methamphetamine (METH)-induced dopaminergic neurotoxicity, and also examined effects of treatment with drugs possessing PPAR gamma agonistic properties. The marked reduction of nuclear PPAR gamma-expressed cells was seen in the striatum 3 days after METH injections (4 mg/kg x 4, i.p. with 2-h interval). The reduction of dopamine transporter (DAT)-positive signals and PPAR gamma expression, and accumulation of activated microglial cells were significantly and dose-dependently attenuated by four injections of a nonsteroidal anti-inflammatory drug and a PPAR gamma ligand, ibuprofen (10 or 20 mg/kg x 4, s.c.) given 30 min prior to each METH injection, but not by either a low or high dose of aspirin. Either treatment of ibuprofen or aspirin, that showed no effects on METH-induced hyperthermia, significantly blocked the METH-induced striatal cyclooxygenase (COX) expression. Furthermore, the treatment of an intrinsic PPAR gamma ligand 15d-PG J2 also attenuated METH injections-induced reduction of striatal DAT. Therefore, the present study suggests the involvement of reduction of PPAR gamma expression in METH-induced neurotoxicity. Taken together with the previous report showing protective effects of other PPAR gamma ligand, these results imply that the protective effects of ibuprofen against METH-induced neurotoxicity may be based, in part, on its anti-inflammatory PPAR gamma agonistic properties, but not on its COX-inhibiting property or hypothermic effect.

    DOI: 10.1007/s11064-008-9863-x

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  • Approaches to Prevent Dopamine Quinone-Induced Neurotoxicity

    Ikuko Miyazaki, Masato Asanuma

    NEUROCHEMICAL RESEARCH   34 ( 4 )   698 - 706   2009年4月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:SPRINGER/PLENUM PUBLISHERS  

    Dopamine (DA) and its metabolites containing two hydroxyl residues exert cytotoxicity in dopaminergic neuronal cells, primarily due to the generation of highly reactive DA and DOPA quinones. Quinone formation is closely linked to other representative hypotheses such as mitochondrial dysfunction, inflammation, oxidative stress, and dysfunction of the ubiquitin-proteasome system, in the pathogenesis of neurodegenerative diseases such as Parkinson&apos;s disease and methamphetamine-induced neurotoxicity. Therefore, pathogenic effects of the DA quinone have focused on dopaminergic neuron-specific oxidative stress. Recently, various studies have demonstrated that some intrinsic molecules and several drugs exert protective effects against DA quinone-induced damage of dopaminergic neurons. In this article, we review recent studies on some neuroprotective approaches against DA quinone-induced dysfunction and/or degeneration of dopaminergic neurons.

    DOI: 10.1007/s11064-008-9843-1

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  • Effects of L-theanine on dopaminergic neuronal cells

    Megumi Someya, Mika Takeshima, Maiko Murata, Ikuko Miyazaki, Masato Asanuma, Taizo Kita

    JOURNAL OF PHARMACOLOGICAL SCIENCES   109   277P - 277P   2009年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:JAPANESE PHARMACOLOGICAL SOC  

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  • 食材および食品に含まれる化学物質の生理活性とその機能―ドパミン神経培養系におけるフィチン酸の作用― 国際誌

    浦添 夏帆, 村田 麻衣子, 青柳 東彦, 安東 勢津子, 宮崎 育子, 浅沼 幹人, 喜多 大三

    九州栄養福祉大学研究紀要   6   75 - 86   2009年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)  

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  • Early changes in astrocytes after rotenone exposure

    Naotaka Kimoto, Saki Fukuoka, Yuri Kikkawa, Francisco. J. Diaz-Corrales, Ikuko Miyazaki, Masato Asanuma

    JOURNAL OF PHARMACOLOGICAL SCIENCES   109   129P - 129P   2009年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:JAPANESE PHARMACOLOGICAL SOC  

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  • Cyclooxygenase-independent neuroprotective effects of aspirin against dopamine quinone-induced neurotoxicity

    Yuri Kikkawa, Naotaka Kimoto, Saki Fukuoka, Ikuko Miyazaki, Masato Asanuma

    JOURNAL OF PHARMACOLOGICAL SCIENCES   109   279P - 279P   2009年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:JAPANESE PHARMACOLOGICAL SOC  

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  • Reactive astrocyte-specific induction of metallothionein in methamphetamine-induced neurotoxicity

    Ikuko Miyazaki, Yuri Kikkawa, Mika Takeshima, Ko Miyoshi, Taizo Kita, Masato Asanuma

    NEUROSCIENCE RESEARCH   65   S256 - S256   2009年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:ELSEVIER IRELAND LTD  

    DOI: 10.1016/j.neures.2009.09.1458

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  • Effects of docosahexaenoic acid on dopaminergic neuronal cells

    Maiko Murata, Mika Takeshima, Megumi Someya, Ikuko Miyazaki, Masato Asanuma, Taizo Kita

    JOURNAL OF PHARMACOLOGICAL SCIENCES   109   278P - 278P   2009年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:JAPANESE PHARMACOLOGICAL SOC  

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  • Analysis of mice carrying a 129 substrain-derived deletion variant in Disc1

    Ko Miyoshi, Kyosuke Kasahara, Ikuko Miyazaki, Masato Asanuma

    NEUROSCIENCE RESEARCH   65   S122 - S122   2009年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:ELSEVIER IRELAND LTD  

    DOI: 10.1016/j.neures.2009.09.577

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  • DOPAMINE-INDUCED BEHAVIORAL CHANGES AND OXIDATIVE STRESS IN METHAMPHETAMINE-INDUCED NEUROTOXICITY

    Taizo Kita, Ikuko Miyazaki, Masato Asanuma, Mika Takeshima, George C. Wagner

    NEW CONCEPTS OF PSYCHOSTIMULANTS INDUCED NEUROTOXICITY   88   43 - 64   2009年

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:ELSEVIER ACADEMIC PRESS INC  

    DOI: 10.1016/S0074-7742(09)88003-3

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  • Involvement of PPAR-gamma in methamphetamine-induced neurotoxicity and protective effect of interferon-gamma 査読

    Fukuoka Saki, Hozumi Hiroaki, Kimoto Naotaka, Kikkawa Yuri, Tsuji Takeshi, Miyazaki Ikuko, Kitamura Yoshihisa, Sendo Toshiaki, Kita Taizo, Asanuma Masato

    JOURNAL OF PHARMACOLOGICAL SCIENCES   109   220P   2009年

  • Effects of dopamine transporter expression on treatment of ACTH in rats 査読

    Emoto Sayaka, Kitamura Yoshihisa, Miyazaki Ikuko, Kitagawa Kouhei, Nagamachi Tomoko, Doi Maho, Ishimaru Yui, Asanuma Masato, Sendo Toshiaki

    JOURNAL OF PHARMACOLOGICAL SCIENCES   109   162P   2009年

  • Dopamine Induces Supernumerary Centrosomes and Subsequent Cell Death through Cdk2 up-Regulation in Dopaminergic Neuronal Cells

    Francisco J. Diaz-Corrales, Masato Asanuma, Ikuko Miyazaki, Ko Miyoshi, Nobutaka Hattori, Norio Ogawa

    NEUROTOXICITY RESEARCH   14 ( 4 )   295 - 305   2008年12月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:SPRINGER  

    Aggregation of proteins in the centrosome is implicated in the pathophysiology of Parkinson&apos;s disease. However, the relevance of the centrosome in neurodegeneration is still obscure. Centrosome duplication is initiated by the cyclin E/cyclin-dependent kinase 2 (Cdk2) complex. The present study determined changes in cyclin E or Cdk2 expression and in the centrosomal structure in dopaminergic neuronal CATH.a cells exposed to 50, 100 and 150 mu M dopamine (DA) for 24 h. DA induced significant increase in Cdk2 protein and cyclin E protein, but not cyclin a mRNA. In DA-treated cells, the intense cyclin E- and Cdk2-immunofluorescence signals were co-localized around large and supernumerary centrosomes, and these two parameters of centrosome amplification were significantly increased compared with the control. Simultaneous co-treatment with DA and a Cdk2 inhibitor blocked centrosome amplification and enhanced cell viability. Our results demonstrated that DA could lead to cyclin E accumulation and Cdk2 up-regulation triggering supernumerary centrosomes and apoptotic cell death.

    DOI: 10.1007/BF03033854

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  • メタンフェタミン急性神経毒性に対するインターフェロン‐γの保護効果発現機序に関する検討

    福岡早紀, 浅沼幹人, 宮崎育子, 穂積宏彰, 吉川友理, 木本直孝, 北村佳久, 千堂年昭, 喜多大三

    日本薬理学雑誌   132 ( 3 )   16P   2008年9月

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    記述言語:日本語  

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  • メタンフェタミン神経毒性に対するインターフェロンγの保護効果におけるペルオキシソーム増殖剤活性化受容体γ(PPARγ)の関与(Possible involvement of peroxisome proliferator-activated receptor-γ in protective effects of interferon-γ against methamphetamine-induced neurotoxicity)

    浅沼 幹人, 福岡 早紀, 穂積 宏彰, 宮崎 育子, 北村 佳久, 千堂 年昭, 喜多 大三

    神経化学   47 ( 2-3 )   237 - 237   2008年8月

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    記述言語:英語   出版者・発行元:日本神経化学会  

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  • Effects of HMGB1 on ischemia-reperfusion injury in the rat heart

    Susumu Oozawa, Shuji Mori, Toru Kanke, Hideo Takahashi, Keyue Liu, Yasuko Tomono, Masato Asanuma, Ikuko Miyazaki, Masahiro Nishibori, Shunji Sano

    CIRCULATION JOURNAL   72 ( 7 )   1178 - 1184   2008年7月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:JAPANESE CIRCULATION SOC  

    Background Coronary ischemia-reperfusion (I/R) injury causes cardiomyocyte necrosis in a multi-step process that includes an inflammatory reaction. A recent study has suggested that high-mobility group box 1 (HMGB 1) is a late mediator of lethal sepsis and an early mediator of inflammation and necrosis following I/R injury. In the present study a neutralizing monoclonal antibody (mAb) for HMGB1 was used to clarify the role of HMGB 1 in cardiac I/R injury.
    Methods and Results Rats underwent 30 min of left coronary artery occlusion followed by 60 min reperfusion. An intravenous injection of anti-HMGB1 mAb or control IgG was administered just before reperfusion. The infarct size was enlarged in the anti-HMGB1 mAb group in comparison with the control group (p&lt;0.05). The treatment of anti-HMGB1 mAb significantly increased the plasma troponin-T and norepinephrine (NE) content in the heart in comparison with the control (p&lt;0.05). Moreover, the production of dihydroxyphenylglycol was reduced in the anti-HMGB1-treated group (p&lt;0.05).
    Conclusion This study shows for the first time the effects of treatment with neutralizing anti-HMGB1 mAb on I/R injury in the rat heart. The findings support the novel view that I/R-induced HMGB1 may be an important factor in the modulation of interstitial NE.

    DOI: 10.1253/circj.72.1178

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  • Dopaminergic neuron-specific oxidative stress caused by dopamine itself

    Ikuko Miyazaki, Masato Asanuma

    ACTA MEDICA OKAYAMA   62 ( 3 )   141 - 150   2008年6月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:OKAYAMA UNIV MED SCHOOL  

    Oxidative stress, including the reactive oxygen or nitrogen species generated in the enzymatical oxidation or auto-oxidation of an excess amount of dopamine, is thought to play an important role in dopaminergic neurotoxicity. Dopamine and its metabolites containing 2 hydroxyl residues exert cytotoxicity in dopaminergic neuronal cells, primarily due to the generation of highly reactive dopamine and DOPA quinones. Dopamine and DOPA quinones may irreversibly alter protein function through the formation of 5-cysteinyl-catechols on the proteins. Furthermore, the quinone formation is closely linked to other representative hypotheses such as mitochondrial dysfunction, inflammation, oxidative stress, and dysfunction of the ubiquitin-proteasome system, in the pathogenesis of neurodegenerative diseases. Therefore, pathogenic effects of the dopamine quinone have recently focused on dopaminergic neuron-specific oxidative stress. In this article, we primarily review recent studies on the pathogenicity of quinone formation, in addition to several neuroprotective approaches against dopamine quinone-induced dysfunction of dopaminergic neurons.

    DOI: 10.18926/AMO/30980

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  • Nonsteroidal anti-inflammatory drugs in experimental parkinsonian models and Parkinson's disease

    Masato Asanuma, Ikuko Miyazaki

    CURRENT PHARMACEUTICAL DESIGN   14 ( 14 )   1428 - 1434   2008年5月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:BENTHAM SCIENCE PUBL LTD  

    A number of experimental studies using parkinsonian models have revealed that nonsteroidal anti-inflammatory drugs (NSAIDs) have neuroprotective properties against dopaminergic neurotoxicity not only by their cyclooxygenase-inhibiting effect but also by other specific properties or some unknown pharmacological effects. This article reviews heterogeneous pharmacological properties of NSAIDs including inhibitory effect against nitric oxide synthesis, agonistic action for peroxisome proliferator-activated receptor or possible suppressive effects against dopamine quinone generation, and also reviews their neuroprotective effects in the experimental parkinsonian models and pathogenesis of Parkinson's disease. Several epidemiological studies recently clarified that the use of nonaspirin NSAIDs but not aspirin was associated with a lower prevalence of Parkinson's disease, in contrast with neuroprotective effects of aspirin in the experimental studies. It also discusses the discrepancy between results in the experimental parkinsonian models and epidemiological data in prevalence of Parkinson's disease on the effects of NSAIDs.

    DOI: 10.2174/138161208784480153

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  • [New perspectives on the mechanism of methamphetamine-induced neurotoxicity]. 査読

    Kita T, Takeshima M, Wagner GC, Hozumi H, Miyazaki I, Asanuma M

    Nihon shinkei seishin yakurigaku zasshi = Japanese journal of psychopharmacology   28 ( 2 )   49 - 61   2008年4月

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    記述言語:日本語  

    PubMed

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  • Specific induction of PAG608 in cranial and spinal motor neurons of L-DOPA-treated parkinsonian rats

    Masako Shimizu, Ikuko Miyazaki, Youichirou Higashi, Maria J. Eslava-Alva, Francisco J. Diaz-Coffales, Masato Asanuma, Norio Ogawa

    NEUROSCIENCE RESEARCH   60 ( 4 )   355 - 363   2008年4月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:ELSEVIER IRELAND LTD  

    We identified p53-activated gene 608 (PAG608) as a specifically induced gene in striatal tissue of L-DOPA (100 mg/kg)-injected hemi-parkinsonian rats using differential display assay. In the present study, we further examined morphological distribution of PAG608 in the central nervous system of L-DOPA-treated hemi-parkinsonian rats. PAG608 expression was markedly induced in fibers and neuronal cells of the lateral globus pallidus and reticular thalamic nucleus adjacent to internal capsule, specifically in the parkinsonian side of L-DOPA-treated models. The protein was also constitutively expressed in motor neurons specifically in either side of the pontine nucleus and motor nuclei of trigeminal and facial nerves. Furthermore, L-DOPA-induced PAG608 expression on motor neurons in the contralateral side of the ventral horn of the spinal cord and the lateral corticospinal tract without cell loss. The specific induction of PAG608 6-48 h after L-DOPA injection in the extrapyramidal tracts, pyramidal tracts and corresponding lower motor neurons of the spinal cords suggests its involvement in molecular events in stimulated motor neurons. Taken together with the constitutive expression of PAG608 in the motor nuclei of cranial nerves, PAG608 may be a useful marker of stressed or activated lower motor neurons. (C) 2007 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

    DOI: 10.1016/j.neures.2007.12.006

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  • Protective effects of interferon-gamma against methamphetamine-induced neurotoxicity

    Hiroaki Hozumi, Masato Asanuma, Ikuko Miyazaki, Saki Fukuoka, Yuri Kikkawa, Naotaka Kimoto, Yoshihisa Kitamura, Toshiaki Sendo, Taizo Kita, Yutaka Gomita

    TOXICOLOGY LETTERS   177 ( 2 )   123 - 129   2008年3月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:ELSEVIER IRELAND LTD  

    Repeated injections of methamphetamine (METH) cause degeneration of striatal dopaminergic nerve terminals. In the present study, we examined the effects of interferon-gamma (IFN-gamma) on METH-induced striatal neurotoxicity in mice. Intraperitoneal injection of IFN-gamma before METH injection significantly prevented METH-induced reduction of striatal dopamine transporter (DAT)-positive signals and hyperthermia. Furthermore, intracerebroventricular injection of IFN-gamma before METH treatment markedly prevented METH-induced reduction of DAT. Interestingly, central IFN-gamma injection had no effect on METH-induced hyperthermia. In addition, IFN-gamma injected centrally after METH treatment, but not systemically, 1 h after the final METH injection significantly protected against METH-induced neurotoxicity. Our results suggest that IFN-gamma injected systemically or its related molecule protects against METH-induced neurotoxicity through intracerebral molecular pathways, while it can prevent METH-induced hyperthermia through different molecular events. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

    DOI: 10.1016/j.toxlet.2008.01.005

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  • Biological roles for neuronal primary cilia

    K. Miyoshi, I. Miyazaki, M. Asanuma

    PSYCHIATRY AND CLINICAL NEUROSCIENCES   62 ( 1 )   S6 - S6   2008年2月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:BLACKWELL PUBLISHING  

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  • Preventing effects of a novel anti-parkinsonian agent zonisamide on dopamine quinone formation

    Masato Asanuma, Ikuko Miyazaki, Francisco J. Diaz-Corrales, Ko Miyoshi, Norio Ogawa, Miho Murata

    NEUROSCIENCE RESEARCH   60 ( 1 )   106 - 113   2008年1月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:ELSEVIER IRELAND LTD  

    The neurotoxicity of dopamine (DA) quinones as dopaminergic neuron-specific oxidative stress is considered to play a role in the pathogenesis and/or progression of Parkinson's disease (PD), since DA quinones conjugate with several key PD pathogenic molecules (e.g., tyrosine hydroxylase, alpha-synuclein and parkin) to form protein-bound quinone (quinoprotein) and consequently inhibit their functions. Zonisamide (ZNS) is used as an anti-epileptic agent but also improved the cardinal symptoms of PD in recent clinical trials in Japan. To evaluate the effects of ZNS on excess cytosolic free DA-induced quinone toxicity, we examined changes in DA quinone-related indices after ZNS treatment both in in vitro cell-free system and in cultured cells. Co-incubation of DA and ZNS in a cell-free system caused conversion of DA to stable melanin via formation of DA-semiquinone radicals and DA chrome. Long-term (5 days) treatment with ZNS decreased quinoprotein and increased DA/DOPA chromes in dopaminergic CATH.a cells. ZNS significantly inhibited quinoprotein formation induced by treatment with tetrahydrobiopterin and ketanserin that elevate cytosolic free DA in the cells. Our results suggest that the novel anti-parkinsonian agent ZNS possesses preventing effects against DA quinone formation induced by excess amount of cytosolic DA outside the synaptic vesicles. (c) 2007 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

    DOI: 10.1016/j.neures.2007.10.002

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  • 食品および食材に含まれる化学物質のモノアミン神経培養系に及ぼす作用に関する研究 国際誌

    村田麻衣子, 竹島美香, 染矢 恵, 宮崎育子, 浅沼幹人, 喜多大三

    九州栄養福祉大学研究紀要   5   55 - 67   2008年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)  

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  • メタンフェタミン神経毒性発現に関する研究の新展開 国際誌

    喜多大三, 竹島美香, Wagner GC, 穂積宏彰, 宮崎育子, 浅沼幹人

    日本神経精神薬理学会雑誌   28   49 - 61   2008年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)  

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  • 小胞外過剰ドパミンによるドパミン神経障害における共通因子としてのキノン体生成 国際誌

    宮崎育子, 浅沼幹人, Diaz-Corrales FJ, 三好 耕, 小川紀雄

    岡山医学会雑誌   119   235 - 239   2008年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)  

    DOI: 10.4044/joma.119.235

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  • Quinone formation as a common factor for dopamine neuron damages by excessive dopamine outside of vesicles 国際誌

    Ikuko Miyazaki, Masato Asanuma, Diaz-Corrales FJ, Ko Miyoshi, Norio Ogawa

    Journal of Okayama Medical Association   119 ( 3 )   235 - 239   2008年

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    記述言語:日本語   掲載種別:研究発表ペーパー・要旨(国際会議)  

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  • メタンフェタミン急性神経毒性に対するインターフェロン‐γの保護効果発現機序に関する検討

    福岡早紀, 浅沼幹人, 宮崎育子, 穂積宏彰, 吉川友理, 木本直孝, 北村佳久, 千堂年昭, 喜多大三

    日本薬理学会近畿部会プログラム・要旨集   113rd   38   2008年

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    記述言語:日本語  

    J-GLOBAL

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  • Effect of baicalin, flavone glucuronide on dopaminergic neuronal cells

    Mika Takeshirna, Yumiko Tanaka, Megurni Someya, Maiko Murata, Ikuko Miyazaki, Masato Asanuma

    JOURNAL OF PHARMACOLOGICAL SCIENCES   106   93P - 93P   2008年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:JAPANESE PHARMACOLOGICAL SOC  

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  • Functional analysis of neuronal cilia using pericentrin mutant mice

    Ko Miyoshi, Kyosuke Kasahara, Ikuko Miyazaki, Masato Asanuma

    NEUROSCIENCE RESEARCH   61   S207 - S207   2008年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:ELSEVIER IRELAND LTD  

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  • Protective effects of interferon-gamma against methamphetamine-induced neurotoxicity

    Hiroaki Hozumi, Masato Asanuma, Ikuko Miyazaki, Saki Fukuoka, Yuri Kikkawa, Naotaka Kimoto, Yoshihisa Kitamura, Toshiaki Sendou, Taizou Kita, Yutaka Gomita

    JOURNAL OF PHARMACOLOGICAL SCIENCES   106   175P - 175P   2008年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:JAPANESE PHARMACOLOGICAL SOC  

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  • テアニンの培養ドパミン神経およびグリア細胞系への作用 国際誌

    染矢 恵, 竹島美香, 村田麻衣子, 宮崎育子, 浅沼幹人, 喜多大三

    九州栄養福祉大学研究紀要   5   69 - 81   2008年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)  

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  • Effects of chronic ACTH treatment on astrocytes and neurogenesis in adult rat hippocampus 査読

    Nagamachi Tomoko, Miyazaki Ikuko, Emoto Sayaka, Do Maho, Kawasaki' Hiromu, Asanuma Masato, Kitamura Yoshihisa, Sendo Toshiaki, Gomita Yutaka

    JOURNAL OF PHARMACOLOGICAL SCIENCES   106   188P   2008年

  • メタンフェタミン神経毒性に関与する炎症・免疫関連分子の網羅的検索

    穂積 宏彰, 宮崎 育子, 喜多 大三, 北村 佳久, 千堂 年昭, 浅沼 幹人, 五味田 裕

    日本神経精神薬理学雑誌 = Japanese journal of psychopharmacology   27 ( 5 )   2007年11月

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    記述言語:日本語  

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  • Protective effects of metallothionein against dopamine quinone-induced dopaminergic neurotoxicity

    Ikuko Miyazaki, Masato Asanuma, Hiroaki Hozumi, Ko Miyoshi, Norio Sogawa

    FEBS LETTERS   581 ( 25 )   5003 - 5008   2007年10月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:ELSEVIER SCIENCE BV  

    Dopamine (DA) quinone as DA neuron-specific oxidative stress conjugates with cysteine residues in functional proteins to form quinoproteins. Here, we examined the effects of cysteine-rich metal-binding proteins, metallothionein (NIT)-1 and -2, on DA quinone-induced neurotoxicity. NIT quenched DA semiquinones in vitro. In dopaminergic cells, DA exposure increased quinoproteins and decreased cell viability; these were ameliorated by pretreatment with MT-inducer zinc. Repeated L-DOPA administration markedly elevated striatal quinoprotein levels and reduced the DA nerve terminals specifically on the lesioned side in NIT-knockout parkinsonian mice, but not in wild-type mice. Our results suggested that intrinsic NIT protects against L-DOPA-induced DA quinone neurotoxicity in parkinsonian mice by its quinone-quenching property. (c) 2007 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.febslet.2007.09.046

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  • Common anti-inflammatory drugs are potentially therapeutic for Parkinson's disease?

    Masato Asanuma, Ikuko Miyazaki

    EXPERIMENTAL NEUROLOGY   206 ( 2 )   172 - 178   2007年8月

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    記述言語:英語   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    DOI: 10.1016/j.expneurol.2007.05.006

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  • メチルフェニデートのドパミン神経毒性に対する作用

    日名俊行, 浅沼幹人, 喜多大三, 宮崎育子, 小川紀雄, 北村佳久, 千堂年昭, 五味田裕

    日本薬学会年会要旨集   127th ( 2 )   129   2007年3月

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    記述言語:日本語  

    J-GLOBAL

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  • Suppression of p53-activated gene, PAG608, attenuates methamphetamine-induced neurotoxicity

    Masato Asanuma, Ikuko Miyazaki, Youichirou Higashi, Francisco J. Diaz-Corrales, Masako Shimizu, Ko Miyoshi, Norio Ogawa

    NEUROSCIENCE LETTERS   414 ( 3 )   263 - 267   2007年3月

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    記述言語:英語   出版者・発行元:ELSEVIER IRELAND LTD  

    The p53-activated gene 608 (PAG608) is a proapoptotic gene activated and regulated by p53 expression in oxidative stress-induced apoptosis of neuronal cells. In this study, we determined the role of PAG608 in methamphetamine-induced neurotoxicity. Treatment of mouse dopaminergic CATH.a cells with 2 mM methamphetamine increased PAG608 expression at 3 h followed by increase in phosphorylated p53 expression. Transient transfection of PAG608 antisense cDNA or RNA interference using PAG608 small interfering RNA significantly attenuated the dose-dependent decrease in cell viability of CATH.a cells by methamphetamine (1-4 mM) exposure. In monoaminergic neuronal B65 cells, which contain serotonin rather than dopamine, methamphetamine-induced cell death was also significantly but partially protected by transient transfection of PAG608 antisense cDNA. Furthermore, cell death of PC 12 cells produced by methamphetamine (1-5 mM) was almost completely prevented by stable expression of PAG608 antisense cDNA, compared with significant reduction of cell viability in control PC12 cells. Our results showed that suppression of PAG608 using transient and stable transfection with PAG608 anti sense cDNA or small interfering RNA attenuates methamphetamine-induced death of various monoaminergic neuronal cells, suggesting that methamphetamine neurotoxicity in monoaminergic cells is related, at least in part, to induction of PAG608 expression. (c) 2006 Elsevier Ireland Ltd. All rights reserved.

    DOI: 10.1016/j.neulet.2006.12.036

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  • 食品容器および食器より溶出する化学物質のドパミン神経障害性に関する研究-ビスフェノールAの培養ドパミン神経系への作用- 国際誌

    喜多大三, 竹島美香, 田中弓子, 宮崎育子, 浅沼幹人

    九州栄養福祉大学研究紀要   4   89 - 97   2007年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)  

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  • Functional analysis of neuronal primary cilia using pericentrin mutant mice

    Ko Miyoshi, Ikuko Miyazaki, Masato Asanuma

    NEUROSCIENCE RESEARCH   58   S123 - S123   2007年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:ELSEVIER IRELAND LTD  

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  • Characterization of pericentrin isoforms in vivo

    Ko Miyoshi, Masato Asanuma, Ikuko Miyazaki, Shinsuke Matsuzaki, Masaya Tohyama, Norio Ogawa

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   351 ( 3 )   745 - 749   2006年12月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    Pericentrin was first identified as a mouse centrosomal protein and is now referred to as pericentrin A. A larger homologous protein in humans with a C-terminal calmodulin-binding domain was later identified as pericentrin B. Pericentrin has been shown to be one of the key components in ciliogenesis.. but in vivo pericentrin products have remained ambiguous. Here we characterized pericentrin isoforms in mice. Two pericentrin transcripts of 9.5 and 6.9 kb were recognized on the mouse tissue Northern blots, while a cRNA probe for a 5'-terminal sequence shared by pericentrin A and B failed to hybridize to the 6.9-kb message. Two pericentrin cDNAs were identified, which encoded pericentrin B and a novel isoform, pericentrin S, sharing with pericentrin B a C-terminal calmodulin-binding motif. Three pericentrin proteins of 360, 255, and 250 kDa revealed by immunoprecipitation analysis were thought to correspond to pericentrin B, pericentrin S, and an unknown N-terminal product. (c) 2006 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.bbrc.2006.10.101

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  • Involvement of STAT3 in bladder smooth muscle hypertrophy following bladder outlet obstruction

    Osamu Fujita, Masato Asanuma, Teruhiko Yokoyama, Ikuko Miyazaki, Norio Ogawa, Hiromi Kumon

    ACTA MEDICA OKAYAMA   60 ( 6 )   299 - 309   2006年12月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:OKAYAMA UNIV MED SCHOOL  

    We examined the involvement of the signal transducer and activator of transcription 3 (STAT3) in bladder outlet obstruction (BOO)-induced bladder smooth muscle hypertrophy using a rat in vivo and in vitro study. BOO induced increases in bladder weight and bladder smooth muscle thickness I week after the operation. By using antibody microarrays, 64 of 389 proteins blotted on the array met our selection criteria of an INR value between &gt;= 2.0 and &lt;= 0.5. This result revealed up-regulation of transcription factors, cell cycle regulatory proteins, apoptosis-associated proteins and so on. On the other hand, down-regulation (INR value &lt;= 0.5) of proteins was not found. In a profiling study, we found an increase in the expression of STAT3. A significant increase in nuclear phosphorylated STAT3 expression was confirmed in bladder smooth muscle tissue by immunohistochemistry and Western blot analysis. Cyclical stretch-relaxation (I Hz) at 120% elongation significantly increased the expression of STAT3 and of alpha-smooth muscle actin in primary cultured bladder smooth muscle cells. Furthermore, the blockade of STAT3 expression by the transfection of STAT3 small interfering RNA (siRNA) significantly prevented the stretch-induced increase in alpha-smooth muscle actin expression. These results suggest that STAT3 has an important role in the induction of bladder smooth muscle hypertrophy.

    DOI: 10.18926/AMO/30724

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  • Embryonic expression of pericentrin suggests universal roles in ciliogenesis

    Ko Miyoshi, Kazunari Onishi, Masato Asanuma, Ikuko Miyazaki, Francisco J. Diaz-Corrales, Norio Ogawa

    DEVELOPMENT GENES AND EVOLUTION   216 ( 9 )   537 - 542   2006年9月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:SPRINGER  

    Pericentrin (Pcnt) is a giant coiled-coil protein known to mediate microtubule organization. It has been recently reported that mitosis-specific centrosomal anchoring of gamma tubulin complexes by Pcnt acts to control mitotic spindle organization, though little is known about the in vivo expression of Pcnt. In this study, we investigated Pcnt expression in mouse embryos. In situ hybridization analysis revealed preferential expression of Pcnt in quiescent G(0) phase cells throughout the embryo with an unexpectedly low expression level in proliferating cells, suggesting that Pcnt might not play an important role in mitotic proliferation. Immunofluorescence analysis confirmed preferential expression of the Pcnt protein in G(0) phase cells. Moreover, Pcnt was shown to be localized to the base of primary cilia in multiple embryonic tissues, in agreement with a recent study demonstrating the involvement of Pcnt in primary cilia formation using cultured mammalian cells.

    DOI: 10.1007/s00427-006-0065-8

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  • Centrosome overduplication induced by rotenone treatment affects the cellular distribution of p53 tumor suppressor protein in the neuroblastoma B65 cell line

    FJ Diaz-Corrales, M Asanuma, Miyazaki, I, K Miyoshi, N Ogawa

    PSYCHIATRY AND CLINICAL NEUROSCIENCES   60   S18 - S26   2006年4月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:BLACKWELL PUBLISHING  

    Recently, the formation of inclusion bodies in several neurodegenerative diseases, including Parkinson's disease, has been associated with the aggregation of unfolded proteins recruited in the centrosome. We have reported previously that rotenone, an insecticide that is used to produce experimental models of Parkinsonism, induced the aggregation of the alpha-synuclein protein in the centrosome, and it notably affected the structure and function of this organelle in primary cultures of mesencephalic neurons and astrocytes. However, it is still obscure the mechanisms through which the disorganization and centrosomal dysfunction could induce cell death. In this study the rat neuroblastoma B65 cell line was chronically exposed to rotenone, and then the distribution of the centrosomal protein gamma-tubulin was studied by immunocytochemistry and Western blot analyses. Finally, the configuration of mitotic spindles and distribution of the p53 protein was observed in the control and rotenone-treated groups. Rotenone treatment increased the number of cells having centrosome overduplication and multipolar mitotic spindles. In contrast, rotenone induced redistribution of the p53 protein, which was colocalized with the gamma-tubulin protein in the perinuclear region of cells having overduplicated centrosomes. In addition, the p53 positive signal was markedly intense in cells containing aberrant chromosome segregation and micronuclei. Our results suggest that centrosome overduplication may play an important role in the redistribution of the p53 protein in rotenone-treated cells, and this could represent an alternative mechanism of rotenone to induce apoptosis in neuronal cells.

    DOI: 10.1111/j.1440-1819.2006.01526.x

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  • Methamphetamine-induced dopaminergic neurotoxicity is regulated by quinone formation-related molecules

    Miyazaki, I, M Asanuma, FJ Diaz-Corrales, M Fukuda, K Kitaichi, K Miyoshi, N Ogawa

    FASEB JOURNAL   20 ( 1 )   571 - +   2006年1月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:FEDERATION AMER SOC EXP BIOL  

    Recently, the neurotoxicity of dopamine (DA) quinone formation by auto-oxidation of DA has focused on dopaminergic neuron-specific oxidative stress. In the present study, we examined DA quinone formation in methamphetamine (METH)-induced dopaminergic neuronal cell death using METH-treated dopaminergic cultured CATH. a cells and METH-injected mouse brain. In CATH. a cells, METH treatment dose-dependently increased the levels of quinoprotein (protein-bound quinone) and the expression of quinone reductase in parallel with neurotoxicity. A similar increase in quinoprotein levels was seen in the striatum of METH (4 mg/kg X4, i.p., 2 h interval)-injected BALB/c mice, coinciding with reduction of DA transporters. Furthermore, pretreatment of CATH. a cells with quinone reductase inducer, butylated hydroxyanisole, significantly and dose-dependently blocked METH-induced elevation of quinoprotein, and ameliorated METH-induced cell death. We also showed the protective effect of tyrosinase, which rapidly oxidizes DA and DA quinone to form stable melanin, against METH-induced dopaminergic neurotoxicity in vitro and in vivo using tyrosinase null mice. Our results indicate that DA quinone formation plays an important role, as a dopaminergic neuron-specific neurotoxic factor, in METH-induced neurotoxicity, which is regulated by quinone formation-related molecules.

    DOI: 10.1096/fj.05-4996fje

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  • Nonsteroidal anti-inflammatory drugs in Parkinson's disease: possible involvement of quinone formation.

    Asanuma, M, Miyazaki, I

    Expert Rev. Neurother.   6   1313 - 1325   2006年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)  

    DOI: 10.1586/14737175.6.9.1313

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  • Specific expression of proapoptotic factor PAG608 on motor neurons in spinal cords of L-DOPA-treated parkinsonian models

    Ikuko Miyazaki, Masako Shimizu, Francisco J. Diaz-Corrales, Maria F. Esraba-Alba, Masato Asanuma

    NEUROSCIENCE RESEARCH   55   S201 - S201   2006年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:ELSEVIER IRELAND LTD  

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  • Pericentrin is localized to the base of neuronal primary cilia in the developing cerebral cortex

    Ko Miyoshi, Ikuko Miyazaki, Masato Asanuma

    NEUROSCIENCE RESEARCH   55   S233 - S233   2006年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:ELSEVIER IRELAND LTD  

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  • L-DOPA treatment from the viewpoint of neuroprotection - Possible mechanism of specific and progressive dopaminergic neuronal death in Parkinson's disease

    N Ogawa, M Asanuma, Miyazaki, I, FJ Diaz-Corrales, K Miyoshi

    JOURNAL OF NEUROLOGY   252   23 - 31   2005年10月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:DR DIETRICH STEINKOPFF VERLAG  

    With regard to the mechanism of selective dopaminergic neuronal death, experimental results of studies on the neurotoxicity of MPTP and rotenone indicate that degeneration of dopamine neurons is closely related to mitochondrial dysfunction, inflammatory process and oxidative stress, particularly with regard to the generation of quinones as dopamine neuron-specific oxidative stress. Thus, it is now clear that the presence of high levels of discompartmentalized free dopamine in sdopaminergic neurons may explain the specific vulnerability of dopaminergic neurons through the generation of highly toxic quinones.

    DOI: 10.1007/s00415-005-4006-7

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  • Prednisolone inhibits proliferation of cultured pulmonary artery smooth muscle cells of patients with idiopathic pulmonary arterial hypertension

    A Ogawa, K Nakamura, H Matsubara, H Fujio, T Ikeda, K Kobayashi, Miyazaki, I, M Asanuma, K Miyaji, D Miura, KF Kusano, H Date, T Ohe

    CIRCULATION   112 ( 12 )   1806 - 1812   2005年9月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

    Background - Idiopathic pulmonary arterial hypertension (IPAH) is associated with proliferation of smooth muscle cells (SMCs) in small pulmonary arteries. There is no therapy that specifically inhibits SMC proliferation. Recent studies reported that prednisolone (PSL) inhibits the postangioplasty proliferation of SMCs in atherosclerotic arteries. In this study, we tested the hypothesis that PSL has antiproliferative effects on pulmonary artery SMCs of patients with IPAH.
    Methods and Results - Pulmonary artery SMCs were harvested from the pulmonary arteries of 6 patients with IPAH who underwent lung transplantation. Control SMCs were obtained from 5 patients with bronchogenic carcinoma who underwent lung lobectomy. After incubation in the presence of platelet-derived growth factor ( PDGF), PSL was added at different concentrations and cell proliferation was assessed by H-3-thymidine incorporation. PSL ( 2 x 10(-4) and 2 x 10(-3) mol/L) significantly inhibited PDGF-stimulated proliferation ( P &lt; 0.05) of SMCs from patients with IPAH but did not affect cell viability of SMCs, as confirmed by trypan blue staining. In cell cycle analysis using a microscope-based multiparameter laser scanning cytometer, PSL inhibited the progression of SMCs from G(0)/G(1) to the S phase. This inhibition was associated with increased p27 expression level. PSL ( 2 x 10(-4) mol/L) also inhibited PDGF-induced SMC migration.
    Conclusions - Our results indicate that PSL has an antiproliferative effect on cultured SMCs of pulmonary arteries from patients with IPAH and suggest that PSL may be potentially useful therapeutically in patients with IPAH.

    DOI: 10.1161/CIRCULATIONHA.105.536169

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  • Pramipexole has ameliorating effects on levodopa-induced abnormal dopamine turnover in parkinsonian striatum and quenching effects on dopamine-semiquinone generated in vitro

    M Asanuma, Miyazaki, I, FJ Diaz-Corrales, M Shimizu, K Tanaka, N Ogawa

    NEUROLOGICAL RESEARCH   27 ( 5 )   533 - 539   2005年7月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:MANEY PUBLISHING  

    Objectives and methods: To clarify the effects of a non-ergot do amine agonist pramipexole on levodopa-induced abnormal dopamine metabolism in the parkinsonian model, we examined striatal changes in dopamine and its metabolites after repeated administration of pramipexole and/or levodopa using 6-hydroxydopamine-lesioned hemi-parkinsonian mice. Moreover, the effects of pramipexole on dopamine-semiquinones were also accessed using an in vitro dopamine-semiquinone generating system to elucidate its neuroprotective property against dopamine quinone-induced neurotoxicity that appears as dopamine neuron-specific oxidative stress.
    Results: Combined administration of pramipexole (0.5 or 1 mg/kg/day, 7 days) selectively suppressed the levodopa-induced (50 mg/kg/day) increase of striatal dopamine turnover in the parkinsonian side, but not in the non-lesioned side. In addition to the antioxidant properties previously reported, it was clarified that pramipexole scavenged dopamine-semiquinones generated in a dose-dependent manner either in simultaneous incubation or post-incubation.
    Discussion: The neurotoxicity of dopamine quinones that appear as dopaminergic neuronspecific oxidative stress has recently been known to play a role in the pathogenesis of Parkinson's disease and neurotoxin-induced parkinsonism. Therefore, the present results revealed that pramipexole possesses neuroprotective effects against abnormal dopamine metabolism in excessively levodopa-administered parkinsonian brains and against cytotoxic dopamine quinones generated from excess dopamine, preventing consequentry dopaminergic neuronal damage induced by excess dopamine or levodopa.

    DOI: 10.1179/016164105X22093

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  • 薬物依存・毒性発現にかかわる分子の分子生物学的検索法─網羅的プロファイリングを中心に. 国際誌

    浅沼幹人, 宮崎育子

    日本薬理学雑誌   126, 30-34   2005年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)  

    DOI: 10.1254/fpj.126.30

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  • Rotenone induces aggregation of gamma-tubulin protein and subsequent disorganization of the centrosome: Relevance to formation of inclusion bodies and neurodegeneration

    FJ Diaz-Corrales, M Asanuma, Miyazaki, I, K Miyoshi, N Ogawa

    NEUROSCIENCE   133 ( 1 )   117 - 135   2005年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    Neurodegenerative disorders are characterized by progressive loss of specific neurons in the central nervous system. Although they have different etiologies and clinical manifestations, most of them share similar histopathologic characteristics such as the presence of inclusion bodies in both neurons and glial cells, which represent intracellular aggregation of misfolded or aberrant proteins. In Parkinson's disease, formation of inclusion bodies has been associated with the aggresome-related process and consequently with the centrosome. However, the significance of the centrosome in the neurodegenerative process remains obscure. In the present study, the morphological and functional changes in the centrosome induced by rotenone, a common insecticide used to produce experimental Parkinsonism, were examined both in vitro and in vivo. Aggregation of gamma-tubulin protein, which is a component of the centrosome matrix and recently identified in Lewy bodies of Parkinson's disease, was observed in primary cultures of mesencephalic cells treated with rotenone. Rotenone-treated neurons and astrocytes showed enlarged and multiple centro-somes. These centrosomes also displayed multiple aggregates of alpha-synuclein protein. Neurons with disorganized centrosomes exhibited neurite retraction and microtubule destabilization, and astrocytes showed disturbances of mitotic spindles. The Golgi apparatus, which is closely related to the centrosome, was dispersed in both rotenone-treated neuronal cells and the substantia nigra of rotenone-treated rats. Our findings suggested that recruitment of abnormal proteins in the centrosome contributed to the formation of inclusion bodies, and that rotenone markedly affected the structure and function of the centrosome with consequent induction of cytoskeleton disturbances, disassembly of the Golgi apparatus and collapse of neuronal cells. (c) 2005 IBRO. Published by Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.neuroscience.2005.01.044

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  • Direct evidence for expression of dopamine receptors in astrocytes from basal ganglia

    Miyazaki, I, M Asanuma, FJ Diaz-Corrales, K Miyoshi, N Ogawa

    BRAIN RESEARCH   1029 ( 1 )   120 - 123   2004年12月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:ELSEVIER SCIENCE BV  

    Expression of dopamine receptors (DA-Rs) in astrocytes was examined in vitro and in vivo using primary cultured astrocytes and brain slices from rat basal ganglia. Astrocytes from basal ganglia expressed DA D1-, D3-, D4- and D5-receptors and D4-mediated signal transduction in response to DA, suggesting possible involvement of astrocytes in the pharmacological action of atypical antipsychotic drugs and in DA response in some neurological diseases. (C) 2004 Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.brainres.2004.09.014

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  • Quinone formation as dopaminergic neuron-specific oxidative stress in the pathogenesis of sporadic Parkinson's disease and neurotoxin-induced parkinsonism

    M Asanuma, Miyazaki, I, FJ Diaz-Corrales, N Ogawa

    ACTA MEDICA OKAYAMA   58 ( 5 )   221 - 233   2004年10月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:OKAYAMA UNIV MED SCHOOL  

    Parkinson's disease (PD) is a progressive neurodegenerative disease characterized by dopaminergic neuron-specific degeneration in the substantia, nigra. A number of gene mutations and deletions have been reported to play a role in the pathogenesis of familial PD. Moreover, a number of pathological and pharmacological studies on sporadic PD and dopaminergic neurotoxin-induced parkinsonism have hypothesized that mitochondrial dysfunction, inflammation, oxidative stress, and dysfunction of the ubiquitin-proteasome system all play important roles in the pathogenesis and progress of PD. However, these hypotheses do not yet fully explain the mechanisms of dopaminergic neuron-specific cell loss in PD. Recently, the neurotoxicity of dopamine quinone formation by auto-oxidation of dopamine has been shown to cause specific cell death of dopaminergic neurons in the pathogenesis of sporadic PD and dopaminergic neurotoxin-induced parkinsonism. Furthermore, this quinone formation is closely linked to other representative hypotheses in the pathogenesis of PD. In this article, we mainly review recent studies on the neurotoxicity of quinone formation as a dopaminergic neuron-specific oxidative stress and its role in the etiology of PD, in addition to several neuroprotective approaches against dopamine quinone-induced toxicity.

    DOI: 10.18926/AMO/32105

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  • Expression of metallothionein-III and cell death in differentiated catecholaminergic neuronal cells

    Y Higashi, M Asanuma, Miyazaki, I, N Ogawa

    NEUROLOGICAL RESEARCH   26 ( 6 )   671 - 676   2004年9月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:MANEY PUBLISHING  

    Metallothionein (MT)-III, an isomer of metallothionein, is also known to be a growth inhibitory factor. MT-III has been reported to decrease the number of surviving neuronal cells in culture medium containing brain extract. Using differentiated catecholaminergic neuronal CATH.a cells treated with dibutyryl cyclic AMP, we examined MT-III expression and the effect of mouse forebrain extract on cell viability. Increase in MT-III expression was revealed in the differentiated cells. Moreover, treatment with mouse forebrain extract induced apoptotic cell death in differentiated CATH.a cells, accompanied by decreases in both MT-III and a neuronal differentiation marker, growth-associated protein-43, expression in surviving cells. These results imply that MT-III expression during the developmental period may be associated with the regulation of normal neural differentiation.

    DOI: 10.1179/016164104225015895

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  • Parkin attenuates manganese-induced dopaminergic cell death

    Y Higashi, M Asanuma, Miyazaki, I, N Hattori, Y Mizuno, N Ogawa

    JOURNAL OF NEUROCHEMISTRY   89 ( 6 )   1490 - 1497   2004年6月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:BLACKWELL PUBLISHING LTD  

    Manganese as environmental factor is considered to cause parkinsonism and induce endoplasmic reticulum stress-mediated dopaminergic cell death. We examined the effects of manganese on parkin, identified as the gene responsible for familial Parkinson's disease, and the role of parkin in manganese-induced neuronal cell death. Manganese dose-dependently induced cell death of dopaminergic SH-SY5Y and CATH.a cells and cholinergic Neuro-2a cells, and that the former two cell types were more sensitive to manganese toxicity than Neuro-2a cells. Moreover, manganese increased the expression of endoplasmic reticulum stress-associated genes, including parkin, in SH-SY5Y cells and CATH.a cells, but not in Neuro-2a cells. Treatment with manganese resulted in accumulation of parkin protein in SH-SY5Y cells and its redistribution to the perinuclear region, especially aggregated Golgi complex, while in Neuro-2a cells neither expression nor redistribution of parkin was noted. Manganese showed no changes in proteasome activities in either cell. Transient transfection of parkin gene inhibited manganese- or manganese plus dopamine-induced cell death of SH-SY5Y cells, but not of Neuro-2a cells. Our results suggest that the attenuating effects of parkin against manganese- or manganese plus dopamine-induced cell death are dopaminergic cell-specific compensatory reactions associated with its accumulation and redistribution to perinuclear regions but not with proteasome system.

    DOI: 10.1111/j.1471-4159.2004.02445.x

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  • DISC1 localizes to the centrosome by binding to kendrin

    K Miyoshi, M Asanuma, Miyazaki, I, FJ Diaz-Corrales, T Katayama, M Tohyama, N Ogawa

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   317 ( 4 )   1195 - 1199   2004年5月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    Disrupted-In-Schizophrenia 1 (DISC1) was identified as a novel gene disrupted by a (1; 11)(q42.1;q 14.3) translocation that segregated with major mental disorders in a Scottish family. Using the yeast two-hybrid system, we screened a human brain cDNA library for interactors of the DISC1 protein. One of the positive clones encoded kendrin/pericentrin-B, a giant protein known to localize specifically to the centrosome. The interaction between DISCI and kendrin in mammalian cells was demonstrated by an immunoprecipitation assay. Residues 446-533 of DISC1 were essential for the interaction with kendrin. Immunocytochemical analysis revealed the colocalization of DISC1 and kendrin to the centrosome. These data indicate that DISC1 localizes to the centrosome by binding to kendrin. Kendrin has been reported to anchor the gamma-tubulin complex to the centrosome, providing microtubule nucleation sites. The present study suggests the possible involvement of DISC1 in the pathophysiology of mental disorders due to its putative effect on centrosomal function. (C) 2004 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.bbrc.2004.03.163

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  • Rotenone induces disassembly of the Golgi apparatus in the rat dopaminergic neuroblastoma B65 cell line

    FJ Diaz-Corrales, M Asanuma, Miyazaki, I, N Ogawa

    NEUROSCIENCE LETTERS   354 ( 1 )   59 - 63   2004年1月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:ELSEVIER SCI IRELAND LTD  

    It has been reported that the Golgi apparatus (GA) is fragmented in some neurodegenerative diseases. However, the significance of the GA fragmentation or disassembly in neurodegeneration is still obscure. To clarify the involvement of this organelle in apoptosis of neuronal cells, we examined the morphological changes in the GA induced by rotenone, a pesticide that produces selective dopaminergic neurodegeneration. In dopaminergic neuroblastoma B65 cells, a 5-day rotenone treatment (50 nM) promoted cell damage. Rotenone-treated cells showed round nuclei, diffuse signals of the GA and cytosolic redistribution of cytochrome c. Nevertheless, these type of cells without nuclear fragmentation did not show any caspase-3 expression. These results indicate that rotenone induces disassembly of the GA in the early stages of the apoptotic process. (C) 2003 Elsevier Ireland Ltd. All rights reserved.

    DOI: 10.1016/j.neulet.2003.09.059

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  • 遺伝子改変によるパーキンソン病モデル. 国際誌

    浅沼幹人, 宮崎育子

    脳の科学   292,165-170   2004年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)  

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  • Specific gene expression and possible involvement of inflammation in methamphetamine-induced neurotoxicity

    M Asanuma, Miyazaki, I, Y Higashi, T Tsuji, N Ogawa

    CURRENT STATUS OF DRUG DEPENDENCE / ABUSE STUDIES: CELLULAR AND MOLECULAR MECHANISMS OF DRUGS OF ABUSE AND NEUROTOXICITY   1025   69 - 75   2004年

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:NEW YORK ACAD SCIENCES  

    To reveal specific gene expression in methamphetamine (METH) -induced dopamine neurotoxicity, temporal characteristics of METH-induced changes in gene expression in dopaminergic neuronal cells were examined using the cDNA array and the differential display method. A number of genes in the class of "trafficking & protein turnover," "metabolic pathways," "transmitters & receptors," and "growth factors, cytokines" were upregulated after the METH treatment in the eDNA array assay. Whereas, some genes related to trafficking & protein turnover and "modulators, effectors & intracellular transducers" were decreased by METH. Some proteins associated with synaptic vesicle transportation indeed up- or downregulated after the METH treatment. These data suggest that the protein trafficking and degradation system is involved in the dopaminergic cell death induced by METH. Furthermore, focusing on inflammatory reactions after METH injection, possible neuroprotective property of nonsteroidal anti-inflammatory drugs were examined against METH-induced neurotoxicity. Coadministration of NSAID with METH significantly attenuated striatal dopamine terminal degeneration and microgliosis induced by METH, suggesting that the protective effects are based on their inhibitory activity on production of cytokines and nitric oxides or their suppressive action against microglia activation.

    DOI: 10.1196/annals.1316.009

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  • ドパミン受容体とトランスポーター. 国際誌

    小川紀雄, 宮崎育子

    脳の科学   292,53-59   2004年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)  

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  • Neuroprotective effects of nonsteroidal anti-inflammatory drugs on neurodegenerative diseases

    M Asanuma, Miyazaki, I, N Ogawa

    CURRENT PHARMACEUTICAL DESIGN   10 ( 6 )   695 - 700   2004年

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:BENTHAM SCIENCE PUBL LTD  

    It is well known that nonsteroidal anti-inflammatory drugs (NSAIDs) possess anti-inflammatory, analgesic and antipyretic properties by inhibiting cyclooxygenase (COX), a prostaglandin-synthesizing enzyme. It has also been revealed that NSAIDs exert inhibitory effects on the generating system of nitric oxide radicals and modulating effects on transcription factors which are related to inflammatory reactions including cytokine expression. Recently, a number of studies have been conducted focusing on the neuroprotective effects of NSAIDs, since it has been reported that inflammatory processes are associated with the pathogenesis of several neurodegenerative diseases including Alzheimer's disease and Parkinson's disease. In the experimental model of Parkinson's disease, NSAIDs have also exerted neuroprotective effects which are based not only on their COX-inhibiting effects but also on other properties: inhibitory effects on nitric oxide synthesis, action as agonists for peroxisome proliferator-activated receptor gamma, and some unknown pharmacological effects. In this article, various pharmacological effects of NSAIDs except their inhibitory action on COX are reviewed, and possible neuroprotective effects of NSAIDs have been discussed on neurodegenerative diseases, especially Parkinson's disease.

    DOI: 10.2174/1381612043453072

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  • 実験的パーキンソニズムに使われる薬剤〜MPTP,6-ヒドロキシドパミンならびにロテノン. 国際誌

    浅沼幹人, 宮崎育子, 小川紀雄

    医薬ジャーナル   40,111-116   2004年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)  

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  • マンガン誘発神経毒性におけるパーキン蛋白のドパミン神経特異的な関与

    宮崎 育子, 浅沼 幹人, 東 洋一郎, 服部 信孝, 水野 美邦, 小川 紀雄

    日本神経精神薬理学雑誌 = Japanese journal of psychopharmacology   23 ( 6 )   2003年12月

  • Methamphetamine-induced neurotoxicity in mouse brain is attenuated by ketoprofen, a non-steroidal anti-inflammatory drug

    M Asanuma, T Tsuji, Miyazaki, I, K Miyoshi, N Ogawa

    NEUROSCIENCE LETTERS   352 ( 1 )   13 - 16   2003年11月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:ELSEVIER SCI IRELAND LTD  

    We examined effects of non-steroidal anti-inflammatory drugs (NSAIDs) on methamphetamine (METH)-induced neurotoxicity. Marked reduction of dopamine transporter-positive signals and accumulation of microglial cells in the striatum after METH injections (4 mg/kg x 4, i.p. with 2 h-interval) were significantly and dose-dependently attenuated by four injections of ketoprofen (2 or 5 mg/kg X 4, s.c.) given 30 min prior to each METH injection, but not by either a low or high dose of aspirin. The present results suggest that the protective effects of ketoprofen against METH-induced neurotoxicity and microgliosis might be based on its inhibitory activity on inflammatory response or on microglia activation, but not on its cyclooxygenase-inhibiting property. This provides a possible new strategy against METH-induced neurotoxicity using commonly used NSAIDs. (C) 2003 Elsevier Ireland Ltd. All rights reserved.

    DOI: 10.1016/S0304-3940(03)01001-2

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  • Overexpression of Cu-Zn superoxide dismutase protects neuroblastoma cells against dopamine cytotoxicity accompanied by increase in their glutathione level

    ME Haque, M Asanuma, Y Higashi, Miyazaki, I, K Tanaka, N Ogawa

    NEUROSCIENCE RESEARCH   47 ( 1 )   31 - 37   2003年9月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:ELSEVIER SCI IRELAND LTD  

    Dopamine (DA) was shown to exert toxic effects on cultured neurons through autoxidation or oxidative deamination, followed by formation of highly reactive quinone compounds and superoxide radicals. In the present study, therefore, any involvement of Cu-Zn superoxide dismutase (SOD) in DA toxicity was evaluated by transfection of Cu-Zn SOD cDNA. The transient transfection of Cu-Zn SOD cDNA inhibited the DA-induced decrease of dopaminergic neuroblastoma cells. Moreover, Cu-Zn SOD cDNA-transfection significantly increased the glutathione (GSH) level when the cells were exposed to DA. However, such Cu-Zn SOD-overexpression failed to show any protective effects against hydrogen peroxide. The Cu-Zn SOD-overexpressing cells also showed significantly higher levels of GSH upon DA exposure than did the empty vector-transfected cells. The increase in the GSH level in response to hydrogen peroxide remained almost identical in empty vector-transfected or Cu-Zn SOD-overexpressed cells. The level of GSH in DA-treated Cu-Zn SOD-overexpressing cells was 2.5-fold higher than that increased by hydrogen peroxide exposure. The catechol structure of DA molecule is probably involved in the mechanism of increasing GSH level. Furthermore, the Cu-Zn SOD-overexpressing cells inhibited the activation of caspase-3 upon DA exposure. Therefore, Cu-Zn SOD overexpression may temporarily inhibit or delay DA autoxidation and consequently increase the GSH level, which then prevents the activation of apoptotic pathway and subsequent cell death. (C) 2003 Elsevier Science Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

    DOI: 10.1016/S0168-0102(03)00166-4

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  • Apoptosis-inducing neurotoxicity of dopamine and its metabolites via reactive quinone generation in neuroblastoma cells

    ME Haque, M Asanuma, Y Higashi, Miyazaki, I, K Tanaka, N Ogawa

    BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS   1619 ( 1 )   39 - 52   2003年1月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:ELSEVIER SCIENCE BV  

    Neurotoxic properties Of L-dopa and dopamine (DA)-related compounds were assessed in human neuroblastoma SH-SY5Y cells with reference to their structural relationship. L-Dopa and its metabolites containing two free hydroxyl residues on their benzene ring showed toxicity in the cell, which was prevented by superoxide dismutase (SOD) and reduced glutathione (GSH), but not by catalase. Furthermore, a synthetic derivative of DA, 3-hydroxy-4-methoxyphenethylamine (HMPE) containing methoxy residue at position 4 in the benzene ring, exerted partial cytotoxicity, which was not prevented by SOD, GSH or catalase. However, the metabolites containing methoxy residue at position 3 failed to show a toxic effect in the SH-SY5Y cells. Moreover, DA induced apoptotic cell death, which was observed by nuclear and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining and measurement of caspase-3 activity; this compound up-regulated apoptotic factor p53 while down-regulating anti-apoptotic factor Bcl-2. In the cell-free in vitro electron spin resonance (ESR) spectrometry, DA possessing two hydroxyl groups showed generation of DA-semiquinone radicals, which were markedly prevented by addition of SOD or GSH but not by catalase. On the other hand, methylation of one of the hydroxyl residues on the benzene ring of DA converted DA to an unoxidizable compound (3-MT or HMPE), and caused it to lose the property to produce serniquinione radicals. It has been previously reported that SOD acting as a superoxide: semiquitione oxidoreductase prevents quinone formation, and that reduced GSH through forming a complex with DA-quinone prevents quinone binding to the thiol group of the intact protein. Therefore, the present results suggest that DA and its metabolites containing two hydroxyl residues exert cytotoxicity mainly due to generation of highly reactive quinones. (C) 2002 Elsevier Science B.V. All rights reserved.

    DOI: 10.1016/S0304-4165(02)00440-3

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  • アルツハイマー病脳で減少しているgrowth inhibitory factor (GIF) の加齢にともなう変化. 国際誌

    浅沼幹人, 宮崎育子, 東 洋一郎, 田中健一, 小川紀雄

    分子精神医学   2003年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)  

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  • 非ステロイド性消炎鎮痛薬の神経保護作用の新展開. 国際誌

    浅沼幹人, 宮崎育子, 辻 武史, 小川紀雄

    日本神経精神薬理学会雑誌   23,111-119   2003年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)  

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  • Dopamine- or L-DOPA-induced neurotoxicity: The role of dopamine quinone formation and tyrosinase in a model of Parkinson's disease

    M Asanuma, Miyazaki, I, N Ogawa

    NEUROTOXICITY RESEARCH   5 ( 3 )   165 - 176   2003年

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:F P GRAHAM PUBLISHING CO  

    Dopamine (DA)- or L-dihydroxyphenylalanine- (L-DOPA-) induced neurotoxicity is thought to be involved not only in adverse reactions induced by long-term L-DOPA therapy but also in the pathogenesis of Parkinson!s disease. Numerous in vitro and in vivo studies concerning DA- or L-DOPA-induced neurotoxicity have been reported in recent decades. The reactive oxygen or nitrogen species generated in the enzymatical oxidation or auto-oxidation of an excess amount of DA induce neuronal damage and/or apoptotic or non-apoptotic cell death; the DA-induced damage is prevented by various intrinsic and extrinsic antioxidants. DA and its metabolites containing two hydroxyl residues exert cytotoxicity in dopaminergic neuronal cells mainly due to the generation of highly reactive DA and DOPA quinones which are dopaminergic neuron-specific cytotoxic molecules. DA and DOPA quinones may irreversibly alter protein function through the formation of 5-cysteinyl-catechols on the proteins. For example, the formation of DA quinone-alpha-synuclein consequently increases cytotoxic protofibrils and the covalent modification of tyrosine hydroxylase by DA quinones. The melanin-synthetic enzyme tyrosinase in the brain may rapidly oxidize excess amounts of cytosolic DA and L-DOPA, thereby preventing slowly progressive cell damage by auto-oxidation of DA, thus maintaning DA levels. Since tyrosinase also possesses catecholamine-synthesizing activity in the absence of tyrosine hydroxylase (TH), the double-edged synthesizing and oxidizing functions of tyrosinase in the dopaminergic system suggest its potential for application in the synthesis of DA, instead of TH in the degeneration of dopaminergic neurons, and in the normalization of abnormal DA turnover in long-term L-DOPA-treated Parkinson's disease patients.

    DOI: 10.1007/BF03033137

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  • ドパミンおよびその誘導体のキノン体生成を介したアポトーシス誘導性. 国際誌

    浅沼幹人, 宮崎育子, Haque ME, 東 洋一郎, 小川紀雄

    Prog Med   2003年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)  

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  • The p53-activated gene, PAG608, requires a zinc finger domain for nuclear localization and oxidative stress-induced

    Y Higashi, M Asanuma, Miyazaki, I, ME Haque, N Fujita, K Tanaka, N Ogawa

    JOURNAL OF BIOLOGICAL CHEMISTRY   277 ( 44 )   42224 - 42232   2002年11月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC  

    The p53-activated gene PAG608, which encodes a nuclear zinc finger protein, is a p53-inducible gene that contributes to p53-mediated apoptosis. However, the mechanisms by which PAG608 is involved in the apoptosis of neuronal cells are still obscure. In this study, we demonstrated that expression of p53 was induced by 100 muM 6-hydroxydopamine (6-OHDA), accompanied by increased PAG608 expression in PC12 cells. On the other hand, transient or permanent transfection of antisense PAG608 cDNA into PC12 cells significantly prevented apoptotic cell death induced by 100 muM 6-OHDA or 200 muM hydrogen peroxide but not by 250 muM 1-methyl-4phenylpyridinium ion. The 6-OHDA-induced activation of caspase-3, DNA fragmentation, loss of mitochondria membrane potential, and induction of p53 and Bax were also prevented in PC12 cells that stably expressed antisense PAG608 cDNA. These results suggest that PAG608 is associated with the apoptotic pathway induced by these oxidative stress-generating reagents, upstream of the collapse in the mitochondrial membrane potential in PC12 cells. Interestingly, transient transfection with PAG608 cDNA increased p53 expression in both PC12 cells and B65 cells, indicating that PAG608 induced by p53 is able to induce p53 expression in these cells inversely. Furthermore, transient transfection of a truncated mutant PAG608 cDNA, lacking the first zinc finger domain, inhibited 6-OHDA-induced cell death and altered the nuclear and nucleolar localization of wild-type PAG608 in PC12 cells. These results suggest that PAG608 may induce or regulate p53 expression and translocate to the nucleus and nucleolus using its first zinc finger domain during oxidative stress-induced apoptosis of catecholamine-containing cells.

    DOI: 10.1074/jbc.M203594200

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  • Age-related changes in expression of metallothionein-III in rat brain

    Miyazaki, I, M Asanuma, Y Higashi, CA Sogawa, K Tanaka, N Ogawa

    NEUROSCIENCE RESEARCH   43 ( 4 )   323 - 333   2002年8月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:ELSEVIER SCI IRELAND LTD  

    Metallothionein (MT)-III is a metal binding protein, called growth inhibitory factor, and is mainly expressed in the central nervous system. Since MT-III decreases in the brain of Alzheimer's disease (AD), a growing interest has been focused on its relationship to neurodegenerative diseases. To clarify age-related changes in the MT-III expression and its inducibility against oxidative stress, we analyzed the expression of MT-III and its mRNA in the brain of lipopolysaccharide (LPS)-treated aged rats. In the frontal cortex, basal expression of MT-III mRNA was significantly increased with aging, while it was observed no induction of MT-III mRNA against LPS administration in the aged rat brain. MT-III immunopositive cells were increased in the frontal, parietal and piriform cortices, hypothalamus and amygdaloid nucleus with aging. The LPS treatment induced MT-III expression in the brain of young-adult rats, but not in the aged rat brain. Furthermore, the MT-III induction with LPS treatment was mainly observed in oligodendrocyte and microglia. In the present study, we showed that inducibility of brain MT-III against oxidative stress may be reduced with aging. Since it has been reported that MT-III has neuroprotective roles as an antioxidant, present results suggest that MT-III is closely related to the neurodegeneration in the aged animals. (C) 2002 Elsevier Science Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

    DOI: 10.1016/S0168-0102(02)00057-3

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  • The dopamine agonist cabergoline provides neuroprotection by activation of the glutathione system and scavenging free radicals

    M Yoshioka, K Tanaka, Miyazaki, I, N Fujita, Y Higashi, M Asanuma, N Ogawa

    NEUROSCIENCE RESEARCH   43 ( 3 )   259 - 267   2002年7月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:ELSEVIER SCI IRELAND LTD  

    Free radicals are involved in the pathogenesis and/or progression of Parkinson's disease (PD). Several ergot derivative dopamine (DA) agonists have been reported to scavenge free radicals in vitro and to show a neuroprotective effect in vivo. We investigated the in vitro free radical scavenging and antioxidant activities of cabergoline, a long-acting ergot DA agonist, as well as its ability to activate glutathione (GSH), catalase (Cat) and superoxide dismutase (SOD) activating effects and its in vivo neuroprotective properties against 6-hydroxydopamine (6-OHDA) intracerebroventricularly (i.c.v.) in mice. The striatal DA turnover induced by i.c.v. injection of 6-OHDA was completely normalized by pretreatment with cabergoline. Moreover, cabergoline scavenged free radicals in vitro and significantly reduced lipid peroxidation in vitro and in vivo. Furthermore, daily administration of cabergoline to mice significantly increased striatal GSH levels by activation of RNA expressions of GSH-related enzymes, although striatal Cat and SOD activities did not change. In addition, our present results suggest that repeated administration of cabergoline attenuates both 6-OHDA-induced nigrostriatal DAergic dysfunction and DA neuronal cell death, since cabergoline also had a neuroprotective effect in the immunohistochemical experiment. In conclusion, our findings indicate that the multiple antioxidant mechanisms of cabergoline, such as activation of the GSH system and the direct free radical scavenging activity, may explain the neuroprotective effect of this ergot DA agonist. (C) 2002 Elsevier Science Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

    DOI: 10.1016/S0168-0102(02)00040-8

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  • Aggravation of 6-hydroxydopamine-induced dopaminergic lesions in metal lothionein-I and -II knock-out mouse brain

    M Asanuma, Miyazaki, I, Y Higashi, K Tanaka, ME Haque, N Fujita, N Ogawa

    NEUROSCIENCE LETTERS   327 ( 1 )   61 - 65   2002年7月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:ELSEVIER SCI IRELAND LTD  

    The effects of two major isoforms of metallothioneins (MTs), MT-I and -II, on dopaminergic neurotoxicity of 6-hydroxydopamine (6-OHDA) were examined using intracerebroventricularly 6-OHDA-injected MT-I, II knock-out (KO) mice. The loss of dopamine neurons in the substantia nigra pars compacta induced by the 6-OHDA injection was significantly aggravated in the MT-I, II KO mice, compared with that in the 6-OHDA-injected wild-type mice. The present results, taken together with the antioxidant properties of MT-I and -II suggest that MT-I and -II exert neuroprotective effects against the dopaminergic neurotoxicity of 6-OHDA at the nigral cell body by scavenging free radicals. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

    DOI: 10.1016/S0304-3940(02)00346-4

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  • Methamphetamine-induced increase in striatal p53 DNA-binding activity is attenuated in Cu,Zn-superoxide dismutase transgenic mice

    M Asanuma, Miyazaki, I, Y Higashi, JL Cadet, N Ogawa

    NEUROSCIENCE LETTERS   325 ( 3 )   191 - 194   2002年6月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:ELSEVIER SCI IRELAND LTD  

    The striatal DNA-binding activities of p53 as a transcription factor were gradually increased at several days after a single methamphetamine (METH) injection, while they were more rapidly increased within several hours after repeated METH injections (x 4 with a 2 h interval). The elevation of striatal p53 DNA-binding after repeated METH injections was markedly attenuated in Cu,Zn-superoxide dismutase transgenic mice, but not affected by treatments with N-methyl-Daspartate or D1 receptor antagonists. The present results suggest that METH-induced production of reactive oxygen species activates striatal p53 DNA-binding activity; this, in turn, may activate other downstream pathways that are responsible for chronic neurotoxicity of METH. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

    DOI: 10.1016/S0304-3940(02)00291-4

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  • Chronic cerebral hypoperfusion induces striatal alterations due to the transient increase of NO production and the depression of glutathione content

    K Tanaka, N Wada-Tanaka, Miyazaki, I, M Nomura, N Ogawa

    NEUROCHEMICAL RESEARCH   27 ( 4 )   331 - 336   2002年4月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:KLUWER ACADEMIC/PLENUM PUBL  

    We examined the effects of chronic cerebral hypoperfusion on the endogenous oxidative stress-related indices, nitrite and nitrate (NOx) concentration. glutathione (GSH) content, superoxide dismutase and catalase activities, and thiobarbituric acid-reactive substances level in the rat striatum, to clarify the participation of oxidative stress in the chronic cerebral hypoperfusion-induced alterations. Our present results indicate that chronic cerebral hypoperfusion produces oxidative stress and disturbs intracellular redox regulation in two distinct phases: at I day, "acute" and at 6 weeks, "chronic" alterations after the operation, Therefore, striatal neural cell damage may be mainly attributed to the transient increase of NOx production at I day after, and the delayed reduction of muscarinic acetylcholine receptor binding in the striatum may be mostly attributed to the continuous depression of GSH content from the 1st to the 6th postoperative week. In particular, the continuous GSH depression may be considered to accompany the pathophysiology of chronic cerebral hypoperfusion.

    DOI: 10.1023/A:1014967414468

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  • GPI1046 prevents dopaminergic dysfunction by activating glutathione system in the mouse striatum

    K Tanaka, M Yoshioka, Miyazaki, I, N Fujita, N Ogawa

    NEUROSCIENCE LETTERS   321 ( 1-2 )   45 - 48   2002年3月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:ELSEVIER SCI IRELAND LTD  

    We investigated both the antioxidant activities of GPI1046, a non-immunosuppressive derivative of FK506, and the in vivo neuroprotective properties against toxicity of intracerebroventricular 6-hydroxydopamine (6-OHDA) in mice. The 6-OHDA-induced reduction in dopamine and its metabolites in the striatum was significantly normalized by daily administration of GPI1046. Moreover, GPI1046 significantly reduced lipid peroxidation in vivo. Further, GPI1046 significantly increased striatal glutathione (GSH) levels by activating GSH synthesis, although the striatal catalase and superoxide dismutase activities did not change. We conclude that GPI1046 may have neuroprotective effects both in cell cultures and in vivo. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

    DOI: 10.1016/S0304-3940(01)02547-2

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  • ニューロメラニン合成酵素チロシナーゼのドパミン神経障害への関与. 国際誌

    浅沼幹人, 東 洋一郎, 宮崎育子, 小川紀雄

    Prog Med   2002年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)  

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  • Neuroprotective effects of non-steroidal anti-inflammatory drugs by direct scavenging of nitric oxide radicals

    M Asanuma, S Nishibayashi-Asanuma, Miyazaki, I, M Kohno, N Ogawa

    JOURNAL OF NEUROCHEMISTRY   76 ( 6 )   1895 - 1904   2001年3月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:BLACKWELL SCIENCE LTD  

    Recently, it has been reported that inflammatory processes are associated with the pathophysiology of Alzheimer's disease and that treatment of non-steroidal anti-inflammatory drugs reduce the risk for Alzheimer's disease. in the present study, we examined nitric oxide radical quenching activity of non-steroidal anti-inflammatory drugs;and steroidal drugs using our established direct in vitro nitric oxide radical detecting system by electron spin resonance spectrometry. The non-steroidal anti-inflammatory drugs, aspirin, mefenamic acid, indomethacin and ketoprofen directly and dose-dependently scavenged generated nitric oxide radicals, in experiments of nitric oxide radical donor, NOC18-induced neuronal damage, these four non-steroidal drugs significantly prevented the NOC18-induced reduction of cell viability and apoptotic nuclear changes in neuronal cells without affecting the induction of inducible nitric oxide synthase-like immunoreactivity. However, ibuprofen, naproxen or steroidal drugs, which had less or no scavenging effects in vitro showed almost no protective effects against NOC18-induced cell toxicity. These results suggest that the protective effects of the former four non-steroidal anti-inflammatory drugs against apoptosis might be mainly due to their direct nitric oxide radical scavenging activities in neuronal cells. These direct NO quenching activities represent novel effects of nonsteroidal anti-inflammatory drugs. Our findings identified novel pharmacological mechanisms of these drugs to exert not only their anti-inflammatory, analgesic, antipyretic activities but also neuroprotective activities against neurodegeneration.

    DOI: 10.1046/j.1471-4159.2001.00205.x

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  • Progressive cortical atrophy after forebrain ischemia in diabetic rats

    F Kondo, M Asanuma, Miyazaki, I, Y Kondo, K Tanaka, H Makino, N Ogawa

    NEUROSCIENCE RESEARCH   39 ( 3 )   339 - 346   2001年3月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:ELSEVIER SCI IRELAND LTD  

    The morphological changes in the brain of diabetic rats were examined up to 8 weeks after transient forebrain ischemia produced by transient occlusion of both carotid arteries. Using histochemistry, we also examined the extent and rate of development of atrophic changes in the brain, appearance of astrocytes, activated microglia, and glucose transporter 1 (GLUT1) in streptozotocin-treated rat brains after forebrain ischemia. Atrophic changes appeared in the hippocampus in both non-diabetic- and diabetic-ischemic groups 4 weeks after ischemia. In diabetic-ischemic rats, the atrophic changes were more severe and progressed more rapidly in the hippocampus, and were also observed in the frontal, temporal and parietal cortices, but not in any cortical areas of the non-diabetic-ischemic rats and non-ischemic-diabetic rats. We observed reduced density of GLUT1 in all corticaI regions and hippocampus in ischemic-diabetic rats at 4-8 weeks, when the number of activated microglias and astroglias increased in all cortical regions. Although severe atrophic changes were observed in the gray matter, no serious injury was noted in the white matter in the diabetic-ischemic group. Our results indicate that brain ischemia in the presence of diabetes causes more severe late-onset damage culminating in brain atrophy, compared with non-diabetics. (C) 2001 Elsevier Science Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

    DOI: 10.1016/S0168-0102(00)00233-9

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  • Localization, regulation, and function of metallothionein-III/growth inhibitory factor in the brain

    CA Sogawa, M Asanuma, N Sogawa, Miyazaki, I, T Nakanishi, H Furuta, N Ogawa

    ACTA MEDICA OKAYAMA   55 ( 1 )   1 - 9   2001年2月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:OKAYAMA UNIV MED SCHOOL  

    The metallothionein (MT) family is a class of low molecular, intracellular, and cysteine-rich proteins with a high affinity for metals. Although the first of these proteins was discovered nearly 40 years ago, their functional significance remains obscure, Four major isoforms (MT-I, MT-II, MT-III, and MT-IV) have been identified in mammals. MT-I and MT-II are ubiquitously expressed in various organs including the brain, while expression of MT-III and MT-IV is restricted in specific organs. MT-III was detected predominantly in the brain, and characterized as a central nervous system-specific isomer, The role of MTs in the central nervous system has become an intense focus of scientific research. An isomer of MTs, MT-III, of particular interest, was originally discovered as a growth inhibitory factor, and has been found to be markedly reduced in the brain of patients with Alzheimer's disease and several other neurodegenerative diseases, MT-III fulfills unique biological roles in homeostasis of the central nervous system and in the etiology of neuropathological disorders.

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  • Molecular mechanism in activation of glutathione system by ropinirole, a selective dopamine D2 agonist

    K Tanaka, Miyazaki, I, N Fujita, ME Haque, M Asanuma, N Ogawa

    NEUROCHEMICAL RESEARCH   26 ( 1 )   31 - 36   2001年1月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:KLUWER ACADEMIC/PLENUM PUBL  

    We have previously reported that ropinirole, a non-ergot dopamine agonist, has neuroprotective effects against h-hydroxydopamine in mice based on in vivo antioxidant properties such as the glutathione (GSH)-activating effect. In the present study, we determined that the effects of ropinirole on the level of expression of GSH-related enzyme mRNA, these enzymes were shown to regulate GSH contents in the brain. This study focused on the mechanism of GSH enhancement by ropinirole. Striatal GSH contents were significantly increased by 7-day daily administration of ropinirole. Furthermore, the expression levels of gamma -glutamylcysteine synthetase (gamma -GCS), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione S-transferase (GST) mRNA increased following daily injections of ropinirole for 7 days. In addition, ropinirole treatment for 7 days suppressed auto-oxidation in mouse striatal homogenates, in contrast to the vehicle treatment. In conclusion, ropinirole was able to suppress auto-oxidation, most probably by increasing GSH levels due to an increase of GSH synthesis. In addition, it is likely that auto-oxidation was also suppressed by the activation of GSH-regulating enzymes such as GPx, GR, and GST in the mouse striatum. Thus, our results indicate that the GSH-activating effect of ropinirole may render this dopamine agonist beneficial as a neuroprotective drug.

    DOI: 10.1023/A:1007672414239

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  • Expression of metallothionein-III mRNA and its regulation by levodopa in the basal ganglia of hemi-parkinsonian rats

    Miyazaki, I, CA Sogawa, M Asanuma, Y Higashi, K Tanaka, T Nakanishi, N Ogawa

    NEUROSCIENCE LETTERS   293 ( 1 )   65 - 68   2000年10月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:ELSEVIER SCI IRELAND LTD  

    In the brain, metallothionein (MT)-III exhibits a free radical scavenging activity. Here we examined the expression of MT-III mRNA in the basal ganglia of 6-hydroxydopamine (6-OHDA)-lesioned hemi-parkinsonian rats and its regulation by levodopa. The level of MT-III mRNA was significantly decreased in the striatum of 6-OHDA-lesioned side. Levodopa treatment significantly increased the expression of striatal MT-III mRNA in the non-lesioned side, but showed no significant effect in the 6-OHDA-lesioned side. These results suggest that the regulation of MT-III mRNA may be related to the progressive degeneration in parkinsonism. (C) 2000 Published by Elsevier Science Ireland Ltd.

    DOI: 10.1016/S0304-3940(00)01488-9

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  • Inhibition of tyrosinase reduces cell viability in catecholaminergic neuronal cells

    Y Higashi, M Asanuma, Miyazaki, I, N Ogawa

    JOURNAL OF NEUROCHEMISTRY   75 ( 4 )   1771 - 1774   2000年10月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

    The biosynthesis of dopamine (DA) in catecholaminergic neurons is regulated by tyrosine hydroxylase, which converts tyrosine into 3,4-dihydroxyphenylalanine (L-DOPA). In melanocytes, tyrosinase catalyzes both the hydroxylation of tyrosine and the consequent oxidation of L-DOPA to form melanin. Although ii has been demonstrated that tyrosinase is also expressed in the brain. the physiological role of tyrosinase in the brain is stilt obscure. In this study. to investigate the role of tyrosinase in catecholaminergic neuronal cells, we examined the effects of tyrosinase inhibition on the viability of CATH,a and SH-SY5Y cells using tyrosinase inhibitors-specifically, phenylthiourea (PTU) and 5-hydroxyindole (5-HI)-and the transfection of antisense tyrosinase cDNA. Both inhibitors significantly reduced the cell viability of CATH.a cells in a dose-dependent manner. PTU also specifically enhanced DA-induced cell death, but 5-HI did not. This discrepancy in cell death is probably due to the inhibitors' different mechanism of action: 5-HI inhibits the hydroxylation or tyrosine as a competitor for the substrate to induce cell death that may be due to depletion of DA, whereas PTU mainly inhibits the enzymatic oxidation of L-DOPA and DA rather than tyrosine hydroxylation to increase consequently autooxidation of DA. Indeed. the intracellular DA content in CATH.a cells was enhanced by PTU exposure. In contrast, PTU showed no enhancing effects on DA-induced cell death of SH-SY5Y cells, which express little tyrosinase. Furthermore. transfection with antisense tyrosinase cDNA into CATH.a cells dramatically reduced cell viability and significantly enhanced DA-induced cell death. These results suggest that tyrosinase controls the intracellular DA content by biosynthesis or enzymatic oxidation of DA, and the dysfunction of this activity induces cell death by elevation of intracellular DA level and consequent gradual autooxidation of DA to generate reactive oxygen species.

    DOI: 10.1046/j.1471-4159.2000.0751771.x

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  • Antioxidants protect against dopamine-induced metallothionein-III (GIF) mRNA expression in mouse glial cell line (VR-2g)

    CA Sogawa, Miyazaki, I, N Sogawa, M Asanuma, N Ogawa, H Furuta

    BRAIN RESEARCH   853 ( 2 )   310 - 316   2000年1月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:ELSEVIER SCIENCE BV  

    Metallothionein (MT)-III, originally discovered as a growth inhibitory factor (GIF), is a brain specific isomer of MTs and is markedly reduced in the brain of patients with Alzheimer's disease (AD) or other neurodegenerative diseases. We analyzed the level and regulation of mRNA expression of MT-III in immortalized fetal mouse brain glial cells (VR-2g) by reverse transcriptase-polymerase chain reaction (RT-PCR). We have recently reported that dopamine (DA) increases the expression of MT-III mRNA in vitro. In this study, we investigated the mechanism of such increase by examining the effects of DA agonists (SKF38393 or bromocriptine) and DA antagonists (SCH23390 or sulpiride) on the expression of MT-III mRNA. MT-III mRNA did not change by either agonist and DA-increased MT-III mRNA was not inhibited by either antagonist. These results suggested that the induction of MT-III mRNA by DA was not mediated by stimulation of DA receptors. On the other hand, DA-induced MT-III mRNA expression was strongly inhibited by the addition of antioxidants (glutathione, vitamin E or ascorbic acid), indicating thar DA-enhanced MT-III mRNA was mediated by reactive oxygen species. Our results suggest that oxidative stress may be one of the principle factors that modulate MT-III mRNA expression. (C) 2000 Elsevier Science B.V. All rights reserved.

    DOI: 10.1016/S0006-8993(99)02284-2

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  • Dopamine D2 receptor-mediated antioxidant and neuroprotective effects of ropinirole, a dopamine agonist

    M Iida, Miyazaki, I, K Tanaka, H Kabuto, E Iwata-Ichikawa, N Ogawa

    BRAIN RESEARCH   838 ( 1-2 )   51 - 59   1999年8月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:ELSEVIER SCIENCE BV  

    Recent information suggests that free radicals are closely involved in the pathogenesis and/or progression of Parkinson's disease (PD). High-dose levodopa therapy has been suggested to increase oxidative stress, thereby accelerating the progression of PD. Based on this viewpoint, free radical scavenging, antioxidant and neuroprotective agents which may prevent the progression of PD have recently attracted considerable attention. For example, ergot derivative dopamine (DA) agonists have been reported to scavenge free radicals in vitro and show a neuroprotective effect in vivo. Non-ergot DA agonists have also recently been used in the treatment of PD despite the lack of substantial evidence for any free radical scavenging activity or antioxidant activity. The present study was conducted to assess the in vitro free radical scavenging and antioxidant activities of ropinirole, a non-ergot DA agonist, as well as its glutathione (GSH), catalase and superoxide dismutase (SOD) activating effects and neuroprotective effect in vivo. Ropinirole scavenges free radicals and suppresses lipid peroxidation in vitro, but these activities are very weak, suggesting that the antioxidant effect of ropinirole observed in vitro may be a minor component of its neuroprotective effect in vivo. Administration of ropinirole for 7 days increased GSH, catalase and SOD activities in the striatum and protected striatal dopaminergic neurons against 6-hydroxydopamine (6-OHDA) in mice. Pre-treatment with sulpiride prevented ropinirole from enhancing striatal GSH, catalase and SOD activities and abolished the protection of dopaminergic neurons against 6-OHDA. Our findings indicate that activation of GSH, catalase and SOB mediated via DA D2 receptors may be the principal mechanism of neuroprotection by ropinirole. (C) 1999 Elsevier Science B.V. All rights reserved.

    DOI: 10.1016/S0006-8993(99)01688-1

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  • Bifemelane hydrochloride protects against cytotoxicity of hydrogen peroxide on cultured rat neuroblastoma cell line

    Miyazaki, I, E Iwata-Ichikawa, M Asanuma, M Iida, N Ogawa

    NEUROCHEMICAL RESEARCH   24 ( 7 )   857 - 860   1999年7月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:KLUWER ACADEMIC/PLENUM PUBL  

    Free radicals are involved in neuronal damage. Bifemelane hydrochloride has been reported to protect neural tissues against ischemic damage and age-related neurodegeneration. We examined the protective effects of bifemelane HCl and the relation between its effectiveness and free radical formation in hydrogen peroxide (H2O2)-induced cytotoxicity using cultured rat neuroblastoma cell line (B50). Cytotoxicity was examined by using the lactate dehydrogenase (LDH) assay and cell viability by the WST-1 assay. H2O2 reduced the survival of B50 cells in a dose-dependent manner, and treatment of these cells with 75 mu M or 100 mu M H2O2 reduced their viability by 50% relative to the control group. B50 cells were treated with 5 or 10 mu M bifemelane for 2 days followed by treatment with 75 mu M or 100 mu M H2O2 H2O2 cytotoxicity was reduced by pretreatment with bifemelane. We also examined the effect of bifemelane on lipid peroxide formation in B50 cells using thiobarbituric acid reactive substances assay. Pretreatment of B50 cells with 10 mu M bifemelane for 2 days reduced lipid peroxide formation to approximately 54% of the control group. Our results suggest that bifemelane hydrochloride provides a protective effect against H2O2 cytotoxicity partly due to its anti-oxidative properties.

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  • Early treatment with cyclosporin A ameliorates the reduction of muscarinic acetylcholine receptors in gerbil hippocampus after transient forebrain ischemia

    Y Kondo, M Asanuma, E Iwata, F Kondo, Miyazaki, I, N Ogawa

    NEUROCHEMICAL RESEARCH   24 ( 1 )   9 - 13   1999年1月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:KLUWER ACADEMIC/PLENUM PUBL  

    Recent evidence has suggested that cyclosporin A (CsA), an immunosuppressive agent, has neuroprotective properties. However, its mechanisms associated with this activity remain unclear. We have previously shown that post-ischemic administration of CsA daily for 14 days prevented the decrease of muscarinic acetylcholine receptor binding in the hippocampus in the gerbil model of 5-min transient forebrain ischemia. In the present study, CsA (5 mg/kg, subcutaneously) was administered to each animal just after, 2 and 6 h after ischemia so as not to exert its immunosuppressive effect. Initial CsA treatment significantly restored the declined muscarinic acetylcholine receptor binding of the hippocampus 14 days after ischemia similar to the previous report. However, CsA. did not alter reactive changes of astrocytes and microglia in the CA1 area of the hippocampus, which had been suppressed by daily administration. These results indicate that CsA could positively modulate the hippocampal acetylcholine neurotransmission system broken down through the ischemia-induced pyramidal cell death and its action mechanism may have no relation to the immunosuppressive properties.

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  • Glial cells protect neurons against oxidative stress via transcriptional up-regulation of the glutathione synthesis

    Emi Iwata-Ichikawa, Yoichi Kondo, Ikuko Miyazaki, Masato Asanuma, Norio Ogawa

    Journal of Neurochemistry   72 ( 6 )   2334 - 2344   1999年

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等  

    We examined the effects of oxidative stress on rat cultured mesencephalic neurons and glial cells. Glial cells were more resistant to 6- hydroxydopamine (6-OHDA) and H2O2 toxicity than neurons. In glial cells, incubation with 6-OHDA and H2O2 induced a significant increase in the expression of γ-glutamylcysteine synthetase (the rate-limiting enzyme in glutathione synthesis) mRNA, which correlated well with increased TPA- response element (TRE)-binding activity. Furthermore, a subsequent elevation in cellular total glutathione content was also observed. In neurons, both agents decreased TRE-binding activity, and these cells failed to up-regulate the glutathione synthesis. We also examined the mechanisms of the neuroprotective effects of glial cells using a gila conditioned medium. Neurons maintained in gila conditioned medium up-regulated the level of TRE- binding activity, γ-glutamylcysteine synthetase mRNA expression, and total glutathione content in response to 6-OHDA or H2O2, and became more resistant to both agents than cells maintained in a normal medium. Neurons maintained in normal medium failed to up-regulate the glutathione synthesis. Our results suggest that transcriptional up-regulation of glutathione synthesis in glial cell appears to mediate brain glial cell resistance against oxidative stress, and that glial cells protect neurons via transcriptional up-regulation of the antioxidant system.

    DOI: 10.1046/j.1471-4159.1999.0722334.x

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  • Protective effects of nicergoline against hydrogen peroxide toxicity in rat neuronal cell line

    E Iwata, Miyazaki, I, M Asanuma, A Iida, N Ogawa

    NEUROSCIENCE LETTERS   251 ( 1 )   49 - 52   1998年7月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:ELSEVIER SCI IRELAND LTD  

    We examined the effects of nicergoline on hydrogen peroxide (H2O2)-induced neurotoxicity in cultured rat neuronal cell line (B50). H2O2 induced death of B50 cells in a dose-dependent manner. The H2O2-induced neuronal cell death was significantly decreased in B50 cells maintained in the presence of nicergoline. We compared the levels of antioxidants (glutathione, catalase and superoxide dismutase) in nicergoline-treated and untreated B50 cells. Lipid peroxidation products (thiobarbituric acid reactive substances, TEARS) levels were also measured. Cultures treated with nicergoline had higher levels of catalase activity. TEARS level was significantly lower in nicergoline-treated cells than in untreated cells. Our results suggest that nicergoline may induce the up-regulation of intracellular antioxidant defences and protect the neuronal cells against oxidative stress. (C) 1998 Elsevier Science ireland Ltd. All rights reserved.

    DOI: 10.1016/S0304-3940(98)00489-3

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  • Effects of repeated cyclosporin A administration on iminodipropionitrile-induced dyskinesia and TRE-/CRE-binding activities in rat brain

    K Iida, E Iwata, M Asanuma, SN Asanuma, M Gomez-Vargas, Miyazaki, I, T Nakanishi, N Ogawa

    NEUROSCIENCE RESEARCH   30 ( 2 )   185 - 193   1998年2月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:ELSEVIER SCI IRELAND LTD  

    To clarify the involvement of immunophilin ligands in the pathogenesis and pathophysiology of dyskinesia, we examined the effects of repeated administration of cyclosporin A (CsA) on rat dyskinesia induced by repeated injection of iminodipropionitrile (IDPN 100 mg/kg, i.p., for 7 days). The addition of CsA treatment (5 mg/kg, s.c., 1 h before each IDPN injection) exacerbated IDPN-induced dyskinesia. In the group treated with both CsA and IDPN, the concentration of dopamine was significantly increased in the striatum and nucleus accumbens compared with the group treated with IDPN alone. Furthermore, in the electrophoretic mobility shift assay, the injection of CsA + IDPN increased binding activities of transcription factors to the TPA (12-O-tetradecanoylphorbol-13-acetate)-responsive element (TRE) and to the cAMP response element (CRE) in the striatum and nucleus accumbens, compared with those in rats treated with IDPN alone. The levels of D-1-receptor mRNA in the striatum were significantly decreased in the IDPN-treated rats but were at the control level in the rats given CsA + IDPN. These findings suggest that the behavioral aggravation of the IDPN-induced dyskinesia caused by CsA administration may be due to the acceleration of the pre- and post-synaptic dopaminegic systems via activation of transcription factors which bind upstream to tyrosine hydroxylase and D-1-receptor genes, and that the immunophilin binding agents such as CsA are involved in this aggravated dyskinesia. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.

    DOI: 10.1016/S0168-0102(97)00128-4

    Web of Science

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    Kondo, Y, Asanuma, M, Kabuto, H, Iwata, E, Kondo, F, Miyazaki, I, Ogawa, N

    J. Brain Sci.   23   250 - 260   1997年

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等  

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  • 母体へのエポキシ樹脂BADGE暴露が新生仔マウス脳にもたらす影響

    宮崎育子, 菊岡 亮, 磯岡奈未, 中山恵利香, 進 浩太郎, 山本大地, Quin E. Kyle, 船越英丸, 禅正和真, 浅沼幹人

    第45回日本毒性学会学術年会  2018年 

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    会議種別:ポスター発表  

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  • 抗うつ薬ミルタザピンによるアストロサイトの5-HT1A受容体を介したメタロチオネイン発現誘導とドパミン神経保護

    菊岡 亮, 宮崎育子, 久保田菜月, 前田恵実, 香川大樹, 守山雅晃, 粂 明日香, 北村佳久, 浅沼幹人

    メタルバイオサイエンス研究会2018  2018年 

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    会議種別:ポスター発表  

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  • 抗鬱薬ミルタザピンの神経ーグリア連関を介したドパミン神経保護効果

    菊岡 亮, 宮崎育子, 久保田菜月, 前田恵実, 香川大樹, 守山雅晃, 粂 明日香, 村上真樹, 北村佳久, 浅沼幹人

    第134回日本薬理学会近畿部会  2018年 

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    会議種別:口頭発表(一般)  

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  • Influence of benzodiazepine medications and GABAA receptor function on the pentobarbital-induced sleep behavior of lipopolysaccharide-treated mice.

    Kitamura, Y, Okada, A, Hongo, S, Otsuki, K, Miki, A, Miyazaki, I, Asanuma, M, Sendo, T

    31st The International College of Neuropsychopharmacology (CINP World Congress)  2018年 

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    記述言語:英語   会議種別:ポスター発表  

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  • Rotigotine protects dopaminergic neurons by targeting serotonin 1A receptors on astrocytes.

    Asanuma, M, Miyazaki, I, Isooka, N, Kikuoka, R, Wada, K, Nakayama, E, Shin, K, Yamamoto, D, Kitamura, Y

    22nd International Congress of Parkinson’s Disease and Movement Disorders  2018年 

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    記述言語:英語   会議種別:ポスター発表  

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  • Involvement of enhanced 5-HT2A receptor function on doxorubicin and cyclophosphamide-induced anxiety-like behavior in rats.

    Naito, N, Kitamura, Y, Nakamura, Y, Sumiyoshi, Y, Kan, S, Miyazaki, I, Asanuma, M, Sendo, T

    31st The International College of Neuropsychopharmacology (CINP World Congress)  2018年 

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    記述言語:英語   会議種別:ポスター発表  

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  • ロテノン誘発神経毒性に対するカフェイン酸,クロロゲン酸の神経保護効果

    磯岡奈未, 和田晃一, 古川智英子, 宮崎育子, 浅沼幹人

    第134回日本薬理学会近畿部会  2018年 

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    会議種別:口頭発表(一般)  

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  • パーキンソン病モデルマウスにおけるメタロチオネインを介したカフェイン酸,クロロゲン酸の神経保護効果

    磯岡奈未, 和田晃一, 古川智英子, 宮崎育子, 浅沼幹人

    メタルバイオサイエンス研究会2018  2018年 

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    会議種別:口頭発表(一般)  

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  • パーキンソン病での神経障害に対するコーヒー成分による腸内環境修飾の影響 招待

    浅沼幹人, 宮崎育子

    全日本コーヒー協会平成28年度研究成果報告会  2017年 

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    会議種別:公開講演,セミナー,チュートリアル,講習,講義等  

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  • 農薬ロテノン暴露による腸管神経障害とコーヒー成分による神経保護.

    宮崎育子, 磯岡奈未, 菊岡 亮, 和田晃一, 北村佳久, 浅沼幹人

    第11回パーキンソン病・運動障害疾患コングレス (MDSJ)  2017年 

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    会議種別:ポスター発表  

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  • Effects of mirtazapine on doxorubicin and cyclophosphamide-induced spatial cognitive impairment and anxiety-like behavior in rats.

    Nakamura, Y, Kitamura, Y, Naito, N, Sumiyoshi, Y, Miyazaki, I, Asanuma, M, Sendo, T

    47th Annual Meeting of Society for Neuroscience (Neuroscience 2017)  2017年 

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    記述言語:英語   会議種別:ポスター発表  

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  • Mirtazapine exerts astrocyte-mediated dopaminergic neuroprotection.

    Kikuoka, R, Miyazaki, I, Kubota, N, Maeda, M, Kagawa, D, Moriyama, M, Kume, A, Murakami, S, Kitamura, Y, Asanuma, M

    47th Annual Meeting of Society for Neuroscience (Neuroscience 2017)  2017年 

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    記述言語:英語   会議種別:ポスター発表  

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  • エポキシ樹脂BADGEの培養神経細胞への影響.

    浅沼幹人, 宮崎育子, 竹島美香, 中山恵利香, 進 浩太郎, Quin E. Kyle

    第44回日本毒性学会学術年会  2017年 

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    会議種別:ポスター発表  

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  • Rotenone-induced dopaminergic neurotoxicity mediated by astrocytes.

    Miyazaki, I, Murakami, S, Kikuoka, R, Isooka, N, Kitamura, Y, Asanuma, M

    第90回日本薬理学会年会  2017年 

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    会議種別:ポスター発表  

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  • Neuroprotective effects of rotigotine in parkinsonian mice.

    sooka, N, Miyazaki, I, Kikuoka, R, Wada, K, Nakayama, E, Yamamoto, D, Shin, K, Kitamura, Y, Asanuma, M

    第90回日本薬理学会年会  2017年 

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  • 妊娠・授乳期におけるエポキシ樹脂暴露の産仔脳1次繊毛への影響.

    浅沼幹人, 宮崎育子, 竹島美香, 村上 真樹, 三好 耕

    第122回日本解剖学会総会・全国学術集会  2017年 

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    会議種別:ポスター発表  

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  • セロトニン1Aアゴニストによる1次繊毛への影響.

    宮崎育子, 磯岡奈未, 粂 明日香, 三好 耕, 浅沼幹人

    第122回日本解剖学会総会・全国学術集会  2017年 

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    会議種別:ポスター発表  

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  • Rotenone induces astrocyte-mediated non-cell autonomous dopaminergic neurotoxicity.

    Miyazaki, I, Murakami, S, Kikuoka, R, Isooka, N, Kitamura, Y, Asanuma, M

    21st International Congress of Parkinson’s Disease and Movement Disorders  2017年 

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    記述言語:英語   会議種別:ポスター発表  

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  • Neuroprotective effects of antidepressant mirtazapine against dopaminergic neurodegeneration in cultured cells and in parkinsonian mice possibly by targeting astrocytes.

    Asanuma, M, Miyazaki, I, Kikuoka, R, Murakami, S, Isooka, N, Kitamura, Y

    21st International Congress of Parkinson’s Disease and Movement Disorders  2017年 

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    記述言語:英語   会議種別:ポスター発表  

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  • 農薬ロテノンによる非細胞自律性ドパミン神経障害.

    宮崎育子, 村上真樹, 菊岡 亮, 磯岡奈未, 北村佳久, 浅沼幹人

    第44回日本毒性学会学術年会  2017年 

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  • 抗うつ薬ミルタザピンのアストロサイトにおけるメタロチオネイン発現誘導およびドパミン神経保護効果.

    菊岡 亮, 宮崎育子, 久保田菜月, 前田恵実, 香川大樹, 守山雅晃, 粂 明日香, 北村佳久, 浅沼幹人

    第27回創薬・薬理フォーラム岡山  2017年 

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    会議種別:口頭発表(一般)  

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  • ロテノン誘発パーキンソン病モデルへのコーヒー成分カフェイン酸,クロロゲン酸投与による神経保護効果.

    磯岡奈未, 和田晃一, 宮崎育子, 菊岡 亮, 浅沼幹人, ロテノン誘発パーキンソン病モデルへのコーヒー成分カフェイン酸, クロロゲン酸投与による神経保護効果

    第27回創薬・薬理フォーラム岡山  2017年 

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    会議種別:口頭発表(一般)  

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  • 農薬ロテノンによる非細胞自律性ドパミン神経障害へのメタロチオネインの関与.

    宮崎育子, 村上真樹, 菊岡 亮, 磯岡奈未, 北村佳久, 十川千春, 十川紀夫, 浅沼幹人

    メタルバイオサイエンス研究会2017  2017年 

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    会議種別:口頭発表(一般)  

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  • Influence of nicotine on doxorubicin and cyclophosphamide-induced spatial cognitive impairment and anxiety-like behavior in rats.

    Kitamura, Y, Sugimoto, M, Kanemoto, E, Machida, A, Nakamura, Y, Miyazaki, I, Asanuma, M, Sendo, T

    47th Annual Meeting of Society for Neuroscience (Neuroscience 2017)  2017年 

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    記述言語:英語   会議種別:ポスター発表  

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  • Rotenone-induced dopaminergic neurotoxicity promoted by mesencephalic astrocyte dysfunction.

    Miyazaki, I, Murakami, S, Kikuoka, R, Isooka, N, Kitamura, Y, Asanuma, M

    23rd World Congress of Neurology  2017年 

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    記述言語:英語   会議種別:ポスター発表  

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  • Neuroprotective effects of rotigotine against dopaminergic neurodegeneration by targeting astrocytes.

    Asanuma, M, Miyazaki, I, Isooka, N, Kikuoka, R, Wada, K, Nakayama, E, Shin, K, Yamamoto, D, Kitamura, Y

    23rd World Congress of Neurology  2017年 

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    記述言語:英語   会議種別:ポスター発表  

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  • クロロゲン酸のPDモデルマウスにおける神経保護効果.

    磯岡奈未, 和田晃一, 宮崎育子, 浅沼幹人

    第39回日本生物学的精神医学会・第47回日本神経精神薬理学会合同年会  2017年 

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    会議種別:ポスター発表  

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  • 農薬ロテノンによるアストロサイト機能異常がもたらすドパミン神経障害.

    宮崎育子, 菊岡 亮, 磯岡奈未, 北村佳久, 浅沼幹人

    第39回日本生物学的精神医学会・第47回日本神経精神薬理学会合同年会  2017年 

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    会議種別:ポスター発表  

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  • アストロサイトを介したミルタザピンのドパミン神経保護に関する検討

    菊岡 亮, 宮崎育子, 久保田菜月, 前田恵実, 香川大樹, 守山雅晃, 粂 明日香, 村上真樹, 北村佳久, 浅沼幹人

    第39回日本生物学的精神医学会・第47回日本神経精神薬理学会合同年会  2017年 

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    会議種別:ポスター発表  

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  • 磯岡奈未, 和田晃一, 宮崎育子, 菊岡 亮, 古川智英子, 浅沼幹人

    ロテノン誘発パーキンソン病モデルにおける腸管神経障害とコーヒー成分による神経保護効果

    第28回創薬薬理フォーラム岡山  2017年 

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    会議種別:口頭発表(一般)  

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  • 磯岡奈未, 和田晃一, 宮崎育子, 古川智英子, 浅沼幹人

    パーキンソン病モデルにおけるコーヒー成分の神経保護効果とメタロチオネイン発現誘導

    メタルバイオサイエンス研究会2017  2017年 

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    会議種別:ポスター発表  

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  • 抗うつ薬ミルタザピンによるアストロサイトのメタロチオネイン発現誘導がもたらすドパミン神経保護

    菊岡 亮, 宮崎育子, 久保田菜月, 前田恵実, 香川大樹, 守山雅晃, 粂 明日香, 北村佳久, 浅沼幹人

    メタルバイオサイエンス研究会2017  2017年 

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    会議種別:口頭発表(一般)  

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  • 農薬ロテノン暴露によるドパミン神経障害におけるアストロサイトの関与.

    第10回パーキンソン病・運動障害疾患コングレス  2016年 

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  • ALSモデルの運動障害および運動神経変性に対するセロトニン1Aアゴニストの抑制効果.

    第10回パーキンソン病・運動障害疾患コングレス  2016年 

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  • 抗うつ薬ミルタザピンのアストロサイトにおけるメタロチオネイン発現誘導およびドパミン神経保護効果.

    メタルバイオサイエンス研究会サテライト2016  2016年 

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  • Serotonin 1A receptors on astrocytes as a target for dopaminergic neuroprotection.

    第89回日本薬理学会年会  2016年 

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  • Neuroprotective effect of fermented papaya preparation (SAIDO-PS501) via activation of astroglial anti-oxidative system.

    第89回日本薬理学会年会  2016年 

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  • Mirtazapine protects dopaminergic neurons via astrocytes.

    第57回日本神経学会学術大会  2016年 

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  • セロトニン1Aアゴニストによるアストロサイト1次繊毛の伸長.

    第121回日本解剖学会総会・全国学術集会  2016年 

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  • 抗うつ薬ミルタザピンのアストロサイトを標的としたドパミン神経保護.

    第46回日本神経精神薬理学会年会  2016年 

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  • 筋萎縮性側索硬化症モデルにおける運動障害および運動神経変性に対する8-OH-DPATの抑制効果.

    第46回日本神経精神薬理学会年会  2016年 

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  • パーキンソン病モデルマウスにおけるミルタザピンの神経保護効果.

    第27回霧島神経薬理フォーラム  2016年 

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  • パーキンソン病モデルマウスにおけるミルタザピンの神経保護効果に関する検討.

    第46回日本神経精神薬理学会年会  2016年 

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  • Neuroprotective profile of mirtazapine on astrocytes in parkinsonian mice.

    第56回日本神経学会学術大会  2015年 

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  • Doxorubicin and cyclophosphamide treatment causes anxiety-like behavior and spatial cognition impairment in rats.

    45th Annual Meeting of Society for Neuroscience (Neuroscience 2015)  2015年 

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  • パーキンソン病モデルマウスにおけるアストロサイトの5-HT1Aレセプターを標的とした神経保護.

    第9回パーキンソン病・運動障害疾患コングレス  2015年 

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  • Effects of nicotine on doxorubicin and cyclophosphamide-induced spatial cognition and anxiety in rats

    45th Annual Meeting of Society for Neuroscience (Neuroscience 2015)  2015年 

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  • パパイア発酵食品のアストロサイトにおけるNrf2活性化作用.

    第88回日本薬理学会年会  2015年 

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  • パーキンソン病モデルマウスにおけるミルタザピンの神経保護効果.

    第88回日本薬理学会年会  2015年 

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  • ミルタザピンのアストロサイトを標的としたドパミン神経保護効果.

    第45回日本神経精神薬理学会 第37回日本生物学的精神医学会  2015年 

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  • L-DOPA uptake into striatal astrocytes in parkinsonian model rats.

    2014年 

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  • Involvement of BDNF in doxorubicin and cyclophosphamide-induced spatial cognition in rats.

    44th Annual Meeting of Society for Neuroscience (Neuroscience 2014)  2014年 

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  • ドパミン欠乏による線条体ニューロンの1次繊毛の伸長.

    第41回日本脳科学会  2014年 

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  • パーキンソン病モデルにおけるアストロサイトでのL-DOPA取り込み.

    第24回日本臨床精神神経薬理学会・第44回日本神経精神薬理学会合同年会,  2014年 

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  • アストロサイトはL-DOPAのリザーバーとなりうる.

    第37回日本神経科学大会  2014年 

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  • ロテノン誘発パーキンソン病モデルマウスの中枢および腸管神経系におけるメタロチオネインの変化.

    第67回日本酸化ストレス学会学術集会  2014年 

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  • ALSモデルマウスにおけるセロトニン1Aアゴニストによる神経保護効果の検討.

    第36回日本生物学的精神医学会 第57回日本神経化学会大会合同年会  2014年 

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  • Disc1遺伝子exon 6に欠損を持つマウスを用いたDisc1の解析.

    第37回日本神経科学大会  2014年 

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  • パーキンソン病モデルマウスにおけるレベチラセタムによる神経保護効果.

    第87回日本薬理学会年会  2014年 

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  • アストロサイトの部位特異的プロファイルがもたらす脳内環境と神経保.

    文部科学省科学研究費補助金[新学術領域研究 脳内環境—恒常性維持機構とその破綻—]平成25年度冬の班会議  2014年 

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  • アストロサイトを介したレベチラセタムのドパミン神経保護効果に関する検討.

    第125回日本薬理学会近畿部会  2014年 

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  • パーキンソン病モデルマウスにおけるレベチラセタムの神経保護とアストロサイトの関与.

    第55回日本神経学会学術大会  2014年 

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  • 農薬ロテノン誘発パーキンソン病モデルマウスにおける中枢および腸管神経障害とメタロチオネインによる神経保護.

    第21回創薬・薬理フォーラム  2014年 

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  • ロテノン皮下投与による中枢・末梢神経系における経時的組織学的変化.

    第125回日本薬理学会近畿部会  2014年 

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  • Neuroprotective effects of levetiracetam in parkinsonian model mice.

    2014年 

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  • Neuroprotective effects of serotonin 1A agonist in ALS model mice.

    2014年 

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  • Analysis of Disc1 using mice carrying a deletion in exon 6 of the Disc1 gene

    2014年 

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  • 創薬標的としてのアストロサイトのメタロチオネイン 招待

    浅沼幹人, 宮崎育子

    メタルバイオサイエンス研究会2013  2013年 

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    会議種別:シンポジウム・ワークショップ パネル(指名)  

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  • Neuroprotective effects of serotoin 1A agonist target astrocytes.

    2013年 

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  • Neuroprotective effects of serotoin 1A agonist target astrocytes.

    XI European Meeting on Glial Cells in Health and Disease  2013年 

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  • ドキソルビシンおよびシクロホスファミド投与ラットにおける精神機能変化および病態機序解明.

    第86回日本薬理学会年会  2013年 

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  • アストロサイトの部位特異的プロファイリングと、その抗酸化防御機構を標的とした神経保護.

    第86回日本薬理学会年会  2013年 

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  • 中枢および末梢神経系におけるロテノンによる神経変性に対するメタロチオネインの関与.

    第86回日本薬理学会年会  2013年 

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  • ACTH反復投与ラットにおける5-HT1A受容体アゴニストの抗うつ効果および海馬神経新生に与える影響.

    第86回日本薬理学会年会  2013年 

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  • セロトニン1Aアゴニストによる神経-アストロサイト連関の修飾

    第36回日本神経科学大会・第56回日本神経化学会大会・第23回日本神経回路学会大会合同大会  2013年 

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  • セロトニン1Aアゴニストによるアストロサイトを標的としたドパミン神経保護.

    第54回日本神経学会学術大会  2013年 

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  • ロテノン神経毒性に対する中枢および末梢神経系のニューロンとグリアの変化とメタロチオネインの関与.

    第36回日本神経科学大会・第56回日本神経化学会大会・第23回日本神経回路学会大会合同大会  2013年 

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  • アストロサイトの部位特異的プロファイルがもたらす脳内環境と神経保護.

    平成24年度新学術領域研究「脳内環境:恒常性維持機構とその破綻」研究班冬の班会議  2013年 

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  • 5-HT1aアゴニスト8-OH-DPATによる神経保護効果はアストロサイトを標的とする.

    第86回日本薬理学会年会  2013年 

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  • アストロサイトの部位特異的プロファイルがもたらす脳内環境と神経保護.

    平成24年度新学術領域研究 「脳内環境:恒常性維持機構とその破綻」研究班冬の班会議  2013年 

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  • 酸化ストレスに対するアストロサイトの神経保護作用における、脳部位特異的プロファイリング.

    第20回創薬・薬理フォーラム岡山  2013年 

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  • Serotonin 1A agonist upregulates metallothionein in astrocytes and protects dopaminergic neurons against oxidative stres.

    第23回日本臨床神経精神薬理学会 第43回日本神経精神薬理学会 合同年会  2013年 

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  • Involvement of the 5-HT1A receptor function in the 8-OH-DPAT treatment on neurogenesis in ACTH-treated rats.

    43rd Annual Meeting of Society for Neuroscience (Neuroscience2013)  2013年 

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  • Involvements of astrocytes and metallothionein in central / peripheral neurodegeneration of environmental toxin-induced parkinsonian model mouse

    第23回日本臨床神経精神薬理学会 第43回日本神経精神薬理学会 合同年会  2013年 

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  • Comparative study of psychological response on treatment with doxorubicin and cyclophosphamide between rats and mice.

    43rd Annual Meeting of Society for Neuroscience (Neuroscience2013)  2013年 

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  • Ketamine exerts antidepressant-like effects during the forced swim test in adrenocorticotropic hormone-treated rats.

    43rd Annual Meeting of Society for Neuroscience (Neuroscience2013)  2013年 

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  • ラットの行動変化から推察する抗がん剤投与による精神機能変化-ドキソルビシンおよびシクロホスファミド投与による影響-.

    第26回日本サイコオンコロジー学会  2013年 

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  • アストロサイトの部位特異的プロファイルがもたらす脳内環境と神経保護.

    平成24年度新学術領域研究 「脳内環境:恒常性維持機構とその破綻」研究班夏の班会議およびワークショップ  2013年 

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  • ニューロンの1次繊毛の解析.

    第40回日本脳科学会  2013年 

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  • 創薬標的としてのアストロサイトのメタロチオネイン.

    メタルバイオサイエンス研究会2013 シンポジウムⅠ:メタロチオネイン研究の新展開 メタロチオネインと疾患、創薬を探る(1)  2013年 

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  • Comprehensive analysis of factors expressed from striatal astrocytes against oxidative stress

    第23回日本臨床神経精神薬理学会 第43回日本神経精神薬理学会 合同年会  2013年 

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  • お茶の旨味成分テアニンの神経保護機構に関する研究 -培養アストログリア細胞におけるテアニンの細胞保護効果について-

    第23回日本臨床神経精神薬理学会 第43回日本神経精神薬理学会 合同年会  2013年 

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  • Astrocytes in the striatum act as a reservoir of L-DOPA but less convert to dopamine.

    XI European Meeting on Glial Cells in Health and Disease  2013年 

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  • Mice carrying a 25-base-pair deletion in exon 6 of the Disc1 gene lack the Disc1 protein.

    第11回世界生物学的精神医学会国際会議 第35回日本生物学的精神医学会 合同大会  2013年 

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  • 抗がん剤投与動物における精神機能および神経新生に関する検討.

    第24回霧島神経薬理フォーラム  2013年 

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  • Disc1に25塩基対の欠損を持つマウスの解析

    第35回日本神経科学大会  2012年 

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  • Rotenone-induced neurotoxicity in enteric and cerebral neuron-glia mixed culture

    第55回日本神経化学会大会・第11回アジア太平洋神経化学会  2012年 

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  • Primary cilia and extra-synaptic neurotransmission

    第55回日本神経化学会大会・第11回アジア太平洋神経化学会  2012年 

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  • ドキソルビシン、シクロホスファミド処置ラットにおける精神障害の評価および解析

    第6回次世代を担う若手医療科学シンポジウム  2012年 

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  • ACTH反復投与ラットにおける5-HT1A受 容体アゴニストの海馬神経新生および細胞内シグナリング伝達系に関する検討

    第6回次世代を担う若手医療科学シンポジウム  2012年 

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  • パーキンソン病モデルマウスにおける5-HT1aアゴニスト8-OH-DPATによる神経保護効果.

    第85回日本薬理学会年会  2012年 

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  • アストロサイトの抗酸化因子の賦活機構と神経保護候補薬剤の探索

    第53回日本神経学会総会  2012年 

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  • 慢性ロテノン曝露の腸管神経叢ニューロンおよびグリアへの影響.

    第85回日本薬理学会年会  2012年 

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  • マウスDisc1遺伝子exon 6の25塩基対の欠損はDisc1タンパクの発現を消失させる

    第34回日本生物学的精神医学会  2012年 

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  • 神経疾患とアストロサイトの抗酸化機構 招待

    宮崎育子

    第21回日本臨床精神神経薬理学会・第41回日本神経精神薬理学会合同年会  2011年 

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    会議種別:シンポジウム・ワークショップ パネル(指名)  

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  • Uptake and metabolism of L-DOPA and dopamine in striatal astrocytes.

    41th Annual Meeting of Society for Neuroscience  2011年 

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  • Effects of rotenone exposure on enteric neuronal or glial cells.

    41th Annual Meeting of Society for Neuroscience  2011年 

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  • L-テアニンのアストログリアでのグルタチオン増加を介したドパミン神経保護効果.

    第64回日本薬理学会西南部会  2011年 

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  • ロテノン曝露パーキンソン病モデルの腸管神経叢における神経障害およびグリア細胞の関与.

    第64回日本薬理学会西南部会  2011年 

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  • ロテノン暴露パーキンソン病モデルの腸管神経叢での神経障害とメタロチオネインの関与.

    メタロチオネインおよびメタルバイオサイエンス研究会2011  2011年 

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  • アストロサイトの抗酸化機構を標的とした神経保護.

    第9回神経科学研究会  2011年 

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  • L-DOPAの初代培養ドパミン神経保護効果およびそれに対する3-OMDの抑制作用はアストロサイトを標的としている.

    第54回日本神経化学会大会  2011年 

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  • ドーパミン受容体は非シナプス性の神経伝達装置である神経細胞1次繊毛に局在する.

    第34回日本神経科学大会  2011年 

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  • ロテノン曝露の腸管神経叢における神経およびグリア細胞への影響.

    第5回パーキンソン病・運動障害疾患コングレス  2011年 

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  • 線条体アストロサイトに取り込まれたL-DOPAの利用効率.

    第54回日本神経化学会大会  2011年 

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  • アストロサイトに取り込まれたL-DOPAおよびドパミンの代謝に関する検討.

    第21回日本臨床精神神経薬理学会・第41回日本神経精神薬理学会  2011年 

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  • 神経精神疾患の治療標的としてのアストロサイト

    第21回日本臨床精神神経薬理学会・第41回日本神経精神薬理学会 合同年会スタディグループ3  2011年 

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  • 培養グリア細胞系におけるメタンフェタミンによる細胞毒性発現.

    第21回日本臨床精神神経薬理学会・第41回日本神経精神薬理学会  2011年 

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  • 非シナプス性の神経伝達装置である神経細胞1次繊毛はドーパミン受容体を発現する.

    第21回日本臨床精神神経薬理学会・第41回日本神経精神薬理学会  2011年 

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  • ドーパミン伝達系とニューロンの1次繊毛の関係.

    第21回日本臨床精神神経薬理学会・第41回日本神経精神薬理学会  2011年 

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  • Effects of electroconvulsive stimuli on neurogenesis in dentate gyrus of ACTH-treated rats

    41th Annual Meeting of Society for Neuroscience  2011年 

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  • Effects of imipramine and lithium on the suppression of cell proliferation in the dentate gyrus of the hippocampus in ACTH-treated rats.

    41th Annual Meeting of Society for Neuroscience  2011年 

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  • 腸管神経叢ニューロンおよびグリアに対するロテノン暴露の影響.

    第34回日本神経科学大会  2011年 

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  • ACTH反復投与ラットにおける海馬細胞新生の減少およびそのメカニズムに関する検討.

    日本薬学会第131年会,学生シンポジウム 創薬を目指す若手薬学研究者の挑戦 -病態モデルと薬効評価による治療戦略への薬理学的展開-  2011年 

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