2022/05/12 更新

写真a

オオモリ イオリ
大守 伊織
OHMORI Iori
所属
教育学域 教授
職名
教授
外部リンク

学位

  • 医学 ( 岡山大学 )

研究キーワード

  • 電位依存性ナトリウムチャネル

  • 発達障害

  • 酸化ストレス

  • 神経分子病態学

  • 小児神経学

  • 神経疾患の病態と治療

  • SCN1A

  • 記憶・学習

  • ドラベ症候群

  • チオレドキシン

  • 慢性腎臓病

  • CACNA1A

  • てんかん

  • 愛着行動

  • 慢性炎症

  • パッチクランプ法

研究分野

  • ライフサイエンス / 胎児医学、小児成育学

  • ライフサイエンス / 生理学

  • ライフサイエンス / 神経科学一般

  • ライフサイエンス / 医療薬学

  • ライフサイエンス / 遺伝学

  • ライフサイエンス / 病態神経科学

  • ライフサイエンス / 遺伝学

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経歴

  • 岡山大学   Institute of Academic and Research, Okayama University   教授

    2017年1月 - 現在

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  • 岡山大学   Graduate School of Education   准教授

    2015年4月 - 2016年12月

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  • 京都大学   医学研究科   特定准教授

    2014年3月 - 2015年3月

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  • 岡山大学   Graduate School of Medicine , Dentistry and Pharmaceutical Sciences   助教

    2005年4月 - 2014年2月

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  • 岡山大学 医歯薬学総合研究科   非常勤研究員

    2004年12月 - 2005年3月

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  • 米国Vanderbilt大学   Dept. of Genetic Medicine

    2003年11月 - 2004年11月

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  • 岡山大学   小児神経科

    1995年4月 - 2003年10月

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所属学協会

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委員歴

  • 日本てんかん学会   評議員  

    2022年   

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  • 日本小児神経学会   国際化推進委員会  

    2021年3月 - 現在   

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    団体区分:学協会

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  • The 13th Asian &Oceanian Epilepsy Congress (AOEC)   発表論文要旨査読  

    2021年1月 - 2021年2月   

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    団体区分:学協会

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  • 日本育療学会第24回学術集会   実行委員  

    2020年8月 - 2020年11月   

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    団体区分:学協会

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  • 日本小児神経学会中国・四国地方会   幹事  

    2019年4月 - 現在   

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    団体区分:学協会

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  • 日本小児神経学会   評議員  

    2016年 - 現在   

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    団体区分:学協会

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  • 日本生理学会   評議員  

    2009年 - 現在   

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    団体区分:学協会

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論文

  • 重度の慢性疾患のある病気療養児に携わる教員が抱える困難と課題 査読

    村上理絵, 大守伊織, 吉利宗久

    発達障害支援システム学研究   20 ( 2 )   65 - 74   2022年1月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  • Txn1 mutation causes epilepsy associated with vacuolar degeneration in the midbrain

    Iori Ohmori, Mamoru Ouchida, Hirohiko Imai, Saeko Ishida, Shinya Toyokuni, Tomoji Mashimo

    bioRxiv   2021年10月

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    担当区分:筆頭著者, 責任著者   記述言語:英語  

    添付ファイル: 2021.10.07.463470v1.full_Txn1.pdf

    DOI: 10.1101/2021.10.07.463470

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  • CUX2 mutations in temporal lobe epilepsy; increased kainate susceptibility and excitatory input to hippocampus in deficient mice

    Toshimitsu Suzuki, Tetsuya Tatsukawa, Genki Sudo, Caroline Delandre, Yun Jin Pai, Hiroyuki Miyamoto, Matthieu Raveau, Atsushi Shimohata, Iori Ohmori, Shin-ichiro Hamano, Kazuhiro Haginoya, Mitsugu Uematsu, Yukitoshi Takahashi, Masafumi Morimoto, Shinji Fujimoto, Hitoshi Osaka, Hirokazu Oguni, Makiko Osawa, Atsushi Ishii, Shinichi Hirose, Sunao Kaneko, Yushi Inoue, Adrian Walton Moore, Kazuhiro Yamakawa

    bioRxiv   2021年9月

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    記述言語:英語   出版者・発行元:Cold Spring Harbor Laboratory  

    <title>Abstract</title><italic>CUX2</italic> gene encodes a transcription factor that controls neuronal proliferation, dendrite branching and synapse formation, locating at the epilepsy-associated chromosomal region 12q24 that we previously identified by a genome-wide association study (GWAS) in Japanese population. A <italic>CUX2</italic> recurrent <italic>de novo</italic> variant p.E590K has been described in patients with rare epileptic encephalopathies and the gene is a candidate for the locus, however the mutation may not be enough to generate the genome-wide significance in the GWAS and whether <italic>CUX2</italic> variants appear in other types of epilepsies and physiopathological mechanisms are remained to be investigated. Here in this study, we conducted targeted sequencings of <italic>CUX2</italic>, a paralog <italic>CUX1</italic> and its short isoform <italic>CASP</italic> harboring a unique C-terminus on 271 Japanese patients with a variety of epilepsies, and found that multiple <italic>CUX2</italic> missense variants, other than the p.E590K, and some <italic>CASP</italic> variants including a deletion, predominantly appeared in patients with temporal lobe epilepsy (TLE). Human cell culture and fly dendritic arborization analyses revealed loss-of- function properties for the <italic>CUX2</italic> variants. <italic>Cux2</italic>- and <italic>Casp</italic>-specific knockout mice both showed high susceptibility to kainate, increased excitatory cell number in the entorhinal cortex, and significant enhancement in glutamatergic synaptic transmission to the hippocampus. CASP and CUX2 proteins physiologically bound to each other and co-expressed in excitatory neurons in brain regions including the entorhinal cortex. These results suggest that <italic>CUX2</italic> and <italic>CASP</italic> variants contribute to the TLE pathology through a facilitation of excitatory synaptic transmission from entorhinal cortex to hippocampus.

    添付ファイル: 2021.09.17.460803v1.full_CUX2.pdf

    DOI: 10.1101/2021.09.17.460803

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  • 性的マイノリティに関する授業が性的マイノリティへの 知識や受容感に及ぼす影響

    野田夕月奈, 山田剛史, 大守 伊織

    岡山大学教師教育開発センター紀要   ( 11 )   75 - 88   2021年

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    担当区分:最終著者   掲載種別:研究論文(大学,研究機関等紀要)  

    添付ファイル: 2021 性的マイノリティに関する授業.pdf

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  • 算数障害生徒への学習支援に関する文献レビュー

    末廣 久美, 大守 伊織

    岡山大学教師教育開発センター紀要   ( 11 )   293 - 306   2021年

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    担当区分:最終著者   掲載種別:研究論文(大学,研究機関等紀要)  

    添付ファイル: 2021 算数障害生徒への学習支援に関する文献レビュー.pdf

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  • Scn1a and Cacna1a mutations mutually alter their original phenotypes in rats 査読 国際誌

    Iori Ohmori, Kiyoka Kobayashi, Mamoru Ouchida

    Neurochemistry International   141   104859 - 104859   2020年12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)   出版者・発行元:Elsevier BV  

    This study aimed to examine the effects of Cacna1a mutation on the phenotype of Scn1a-associated epilepsy in rats. We used rats with an N1417H missense mutation in the Scn1a gene and others with an M251K mutation in the Cacna1a gene. Scn1a/Cacna1a double mutant rats were generated by mating both Scn1a and Cacna1a mutants. We investigated general health and the epileptic phenotype in all these genotypes. The onset threshold of hyperthermia-induced seizures was examined at 5 weeks and spontaneous seizures were monitored using video-EEG recordings from 6 to 12 weeks of age. Scn1a/Cacna1a double mutants showed significantly reduced threshold for hyperthermia-sensitive seizures onset compared with the Scn1a mutants and had absence seizures having 6-7 c/s spike-wave bursts with changes in the spike-wave pattern, whereas Cacna1a mutants had regular 6-7 c/s spike-wave bursts. In Scn1a/Cacna1a double mutants, 6-7 c/s spike-wave bursts were accompanied with eyelid myoclonia and continuously shifting generalized clonic seizures, which were not observed in either Scn1a or Cacna1a mutants. Although a curvature of the spine was observed in rats of all these genotypes, the degree of curvature was more pronounced in Scn1a/Cacna1a double mutants, followed by Cacna1a and Scn1a mutants. Our results indicate that Cacna1a and Scn1a mutations mutually alter their original phenotypes in rats. The phenotype of absence seizures with eyelid myoclonia, generalized clonic seizures, and of spine curvature in the Scn1a/Cacna1a double mutants were similar to that observed in patients with Dravet syndrome.

    添付ファイル: 2020 Scn1a and Cacna1a mutations mutually alter their original phenotypes in rats.pdf

    DOI: 10.1016/j.neuint.2020.104859

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  • A recurrent PJA1 variant in trigonocephaly and neurodevelopmental disorders 査読 国際誌

    Toshimitsu Suzuki, Toshifumi Suzuki, Matthieu Raveau, Noriko Miyake, Genki Sudo, Yoshinori Tsurusaki, Takaki Watanabe, Yuki Sugaya, Tetsuya Tatsukawa, Emi Mazaki, Atsushi Shimohata, Itaru Kushima, Branko Aleksic, Tomoko Shiino, Tomoko Toyota, Yoshimi Iwayama, Kentaro Nakaoka, Iori Ohmori, Aya Sasaki, Ken Watanabe, Shinichi Hirose, Sunao Kaneko, Yushi Inoue, Takeo Yoshikawa, Norio Ozaki, Masanobu Kano, Takeyoshi Shimoji, Naomichi Matsumoto, Kazuhiro Yamakawa

    Annals of Clinical and Translational Neurology   7 ( 7 )   1117 - 1131   2020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:Wiley  

    OBJECTIVE: Neurodevelopmental disorders (NDDs) often associate with epilepsy or craniofacial malformations. Recent large-scale DNA analyses identified hundreds of candidate genes for NDDs, but a large portion of the cases still remain unexplained. We aimed to identify novel candidate genes for NDDs. METHODS: We performed exome sequencing of 95 patients with NDDs including 51 with trigonocephaly and subsequent targeted sequencing of additional 463 NDD patients, functional analyses of variant in vitro, and evaluations of autism spectrum disorder (ASD)-like phenotypes and seizure-related phenotypes in vivo. RESULTS: We identified de novo truncation variants in nine novel genes; CYP1A1, C14orf119, FLI1, CYB5R4, SEL1L2, RAB11FIP2, ZMYND8, ZNF143, and MSX2. MSX2 variants have been described in patients with cranial malformations, and our present patient with the MSX2 de novo truncation variant showed cranial meningocele and partial epilepsy. MSX2 protein is known to be ubiquitinated by an E3 ubiquitin ligase PJA1, and interestingly we found a PJA1 hemizygous p.Arg376Cys variant recurrently in seven Japanese NDD patients; five with trigonocephaly and one with partial epilepsy, and the variant was absent in 886 Japanese control individuals. Pja1 knock-in mice carrying p.Arg365Cys, which is equivalent to p.Arg376Cys in human, showed a significant decrease in PJA1 protein amount, suggesting a loss-of-function effect of the variant. Pja1 knockout mice displayed moderate deficits in isolation-induced ultrasonic vocalizations and increased seizure susceptibility to pentylenetetrazole. INTERPRETATION: These findings propose novel candidate genes including PJA1 and MSX2 for NDDs associated with craniofacial abnormalities and/or epilepsy.

    添付ファイル: 2020 A recurrent PJA1 variant in trigonocephaly and neurodevelopmental disorders.pdf

    DOI: 10.1002/acn3.51093

    PubMed

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    その他リンク: https://onlinelibrary.wiley.com/doi/full-xml/10.1002/acn3.51093

  • Poor mother–offspring relationships in rats with Cacna1a mutation 査読

    Kawakami N, Kobayashi K, Nishimura A, Ohmori I

    Experimental Animals   24 ( 69 )   153 - 160   2020年4月

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    担当区分:最終著者, 責任著者   記述言語:英語  

    添付ファイル: 2020 Poor mother-offspring relationships in rats with Cacna1a mutation.pdf

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  • Action of antiepileptic drugs on neuron 査読

    Kobayashi K, Endoh F, Ohmori I, Akiyama T

    Brain Dev.   42 ( 1 )   2 - 5   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)  

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  • 学校教員や心理職になり得る大学生の性的マイノリティへの態度に及ぼす講義の効果 査読

    佐々木新, 大守伊織

    GID(性同一性障害)学会雑誌   ( 13 )   67 - 73   2020年

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    担当区分:最終著者   掲載種別:研究論文(学術雑誌)  

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  • 映画「私の中のあなた」から考える 終末期小児がんの 子どもと家族がより良く生きるための支援

    大守伊織, 水谷有

    岡山大学大学院教育学研究科研究集録   ( 174 )   15 - 23   2020年

  • ADHD患児とその保護者の服薬アドヒアランス調査

    大守伊織, 南 恭子, 大野繁, 岡牧郎

    岡山大学大学院教育学研究科研究集録   ( 174 )   9 - 14   2020年

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    担当区分:筆頭著者, 責任著者  

    添付ファイル: 2020 ADHD患児とその保護者の服薬アドヒアランス調査.pdf

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  • PRRT2 mutations in Japanease patients with benign infantile epilepsy and paroxysmal kinesigenic dyskinesia 査読 国際誌

    Okumura A, Shimojima K, Kurahashi H, Numoto S, Shimada S, Ishii A, Ohmori I, Takahashi S, Awaya T, Kubota T, Sakakibara T, Ishihara N, Hattori A, Torisu H, Tohyama J, Inoue T, Haibara A, Nishida T, Yuhara Y, Miya K, Tanaka R, Hirose S, Yamamoto T

    Seizure   71   1 - 5   2019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)  

    DOI: 10.1016/j.seizure.2019.05.017

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  • 性別違和をもつ患者の診療録から見える 学校生活場面での困難さ 査読

    天野佑美, 佐々木新, 松本洋輔, 大守伊織

    兵庫教育大学 教育実践学論集   ( 20 )   39 - 48   2019年3月

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

    添付ファイル: 2019 性別違和をもつ患者の診療録から見える格好生活場面での困難さ.pdf

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  • 学校教員や心理職になり得る大学生の性的マイノリティへの態度と関連する要因 査読

    佐々木新, 大守伊織

    GID(性同一性障害)学会雑誌   ( 12 )   41 - 49   2019年

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    担当区分:最終著者   掲載種別:研究論文(学術雑誌)  

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  • 成人期以降の性的マイノリティ当事者が 学校生活を振り返って,学校教育に求めること

    佐々木新, 天野佑美, 大守伊織

    岡山大学大学院教育学研究科研究集録   ( 171 )   39 - 46   2019年

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    担当区分:最終著者  

    添付ファイル: 2019 成人期以降の性的マイノリティ当事者.pdf

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  • 年齢依存性てんかん性脳症の分子病態解析

    大内田守, 真下知士, 豊國伸哉, 大守伊織

    てんかん治療研究振興財団   30   37 - 44   2019年

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    担当区分:最終著者   掲載種別:研究論文(その他学術会議資料等)  

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  • 同性婚は日本で容認されるか? ─ 他国の同性婚容認を参考に ─

    大守伊織, 天川あかり

    岡山大学大学院教育学研究科研究集録   2019年

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    担当区分:筆頭著者, 責任著者  

    添付ファイル: 2019 同性婚は日本で容認されるか?.pdf

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  • 性的マイノリティ当事者の語りは聴き手の性的マイノリティへの印象や 当惑感を改善する 査読

    前本浩希, 佐々木新, 大守伊織

    GID (性同一性障害) 学会雑誌   ( 12 )   103 - 110   2019年

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

    添付ファイル: 2019_性的マイノリティ当事者の語り fulltext20211005-1.pdf

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  • Trends in research concerning school re-entry support for children with chronic illness.

    Murakami R, Ohmori I

    Bulletin of center for teacher education   8   181 - 191   2018年

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    担当区分:最終著者   記述言語:英語   掲載種別:研究論文(大学,研究機関等紀要)  

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  • A case of Dravet syndrome with cortical myoclonus indicated by jerk-locked back-averaging of electroencephalogram data 査読

    Yoshinori Kobayashi, Yoshiyuki Hanaoka, Tomoyuki Akiayma, Iori Ohmori, Mamoru Ouchida, Toshiyuki Yamamoto, Makio Oka, Harumi Yoshinaga, Katsuhiro Kobayashi

    BRAIN & DEVELOPMENT   39 ( 1 )   75 - 79   2017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  

    We report a female patient with Dravet syndrome (DS) with erratic segmental myoclonus, the origin of which was first identified in the cerebral cortex by the detection of myoclonus-associated cortical discharges. The discharges were disclosed through jerk locked back-averaging of electroencephalogram (EEG) data using the muscle activity of myoclonus as triggers. The detected spikes on the contralateral parieto-central region preceded myoclonic muscle activity in the forearms by 28-46 ms. The patient was six months old at the time of examination, and was developing normally before seizure onset at two months of age. She suffered from recurrent afebrile or febrile generalized tonic clonic seizures that often developed into status epilepticus. Interictal EEG and brain magnetic resonance imaging (MRI) showed no significant findings. The amplitudes of the somatosensory-evoked potentials were not extremely large. She has a chromosomal microdeletion involving SCN1A and adjacent genes. (C) 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.braindev.2016.07.005

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  • Cytokine-related and sodium channel polymorphism as candidate predisposing factors for childhood encephalopathy FIRES/AERRPS 査読

    M. Saitoh, K. Kobayashi, I. Ohmori, Y. Tanaka, K. Tanaka, T. Inoue, A. Horino, K. Ohmura, A. Kumakura, Y. Takei, S. Hirabayashi, M. Kajimoto, T. Uchida, S. Yamazaki, T. Shiihara, T. Kumagai, M. Kasai, H. Terashima, M. Kubota, M. Mizuguchi

    JOURNAL OF THE NEUROLOGICAL SCIENCES   368   272 - 276   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:ELSEVIER SCIENCE BV  

    Febrile infection-related epilepsy syndrome (FIRES), or acute encephalitis with refractory, repetitive partial seizures (AERRPS), is an epileptic encephalopathy beginning with fever-mediated seizures. The etiology remains unclear. To elucidate the genetic background of FIRES/AERRPS (hereafter FIRES), we recruited 19 Japanese patients, genotyped polymorphisms of the IL1B, IL6, IL10, TNFA, IL1RN, SCN1A and SCN2A genes, and compared their frequency between the patients and controls. For IL1RN, the frequency of a variable number of tandem repeat (VNTR) allele, RN2, was significantly higher in the patients than in controls (p = 0.0067), and A allele at rs4251981 in 5' upstream of IL1RN with borderline significance (p = 0.015). Haplotype containing RN2 was associated with an increased risk of FIRES (OR 3.88, 95%CI 1.40-10.8, p = 0.0057). For SCN1A, no polymorphisms showed a significant association, whereas a missense mutation, R1575C, was found in two patients. For SCN2A, the minor allele frequency of G allele at rs1864885 was higher in patients with borderline significance (p = 0.011).
    We demonstrated the association of IL1RN haplotype containing RN2 with FIRES, and showed a possible association of IL1RN rs4251981 G &gt; A and SCN2A rs1864885 A &gt; G, in Japanese patients. These preliminary findings suggest the involvement of multiple genetic factors in FIRES, which needs to be confirmed by future studies in a larger number of FIRES cases. (C) 2016 Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.jns.2016.07.040

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  • 医療機器を用いた臨床研究実施に関するアンケート調査結果 査読

    清水公治, 伊藤達也, 岩江荘介, 大守伊織, 倉田真由美, 住谷昌彦, 戸高浩司, 村山敏典, 山本 晴子, 川上浩司

    医療機器学   86 ( 5 )   482 - 488   2016年

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    記述言語:日本語   出版者・発行元:一般社団法人日本医療機器学会  

    DOI: 10.4286/jjmi.86.482

    CiNii Article

    CiNii Books

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    その他リンク: http://search.jamas.or.jp/link/ui/2017045190

  • Action potentials contribute to epileptic high-frequency oscillations recorded with electrodes remote from neurons 査読

    Katsuhiro Kobayashi, Tomoyuki Akiyama, Iori Ohmori, Harumi Yoshinaga, Jean Gotman

    CLINICAL NEUROPHYSIOLOGY   126 ( 5 )   873 - 881   2015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:ELSEVIER IRELAND LTD  

    Objective: The importance of epileptic high-frequency oscillations (HFOs) in electroencephalogram (EEG) is growing. Action potentials generating some HFOs are observed in the vicinity of neurons in experimental animals. However electrodes that are remote from neurons, as in case of clinical situations, should not record action potentials. We propose to resolve this question by a realistic simulation of epileptic neuronal network.
    Methods: The rat dentate gyrus with sclerosis was simulated in silico. We computed the current dipole moment generated by each granule cell and the field potentials in a measurement area far from neurons.
    Results: The dentate gyrus was stimulated through synaptic input to evoke discharges resembling interictal epileptiform discharges, which had superimposed HFOs &lt;= 295 Hz that were recordable with remote electrodes and represented bursts of action potentials of granule cells. The increase in power of HFOs was associated with the progression of sclerosis, the reduction of GABAergic inhibition, and the increase in cell connectivity. Spectral frequency of HFOs had similar tendencies.
    Conclusions: HFOs recorded with electrodes remote from neurons could actually be generated by clusters of action potentials. Significance: The phenomenon of action potentials recorded with remote electrodes can possibly extend the clinical meaning of EEG. (C) 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

    DOI: 10.1016/j.clinph.2014.08.010

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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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    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: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.

    添付ファイル: 2014 Methylphenidate improves learning_Epilepsia.pdf

    DOI: 10.1111/epi.12750

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  • 遺伝学的検査をめぐる国際動向―欧米と中国の動き 査読

    岩江荘介, 大守伊織, 小杉眞司

    こころの科学「遺伝診断の未来と罠」pp.58-63 日本評論社   58 - 63   2014年9月

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  • The transdermal inhibition of melanogenesis by a cell-membrane-permeable peptide delivery system based on poly-arginine 査読

    Nanako Ookubo, Hiroyuki Michiue, Mizuki Kitamatsu, Maho Kamamura, Tei-ichi Nishiki, Iori Ohmori, Hideki Matsui

    BIOMATERIALS   35 ( 15 )   4508 - 4516   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:ELSEVIER SCI LTD  

    Topical therapy is the most favored form of treatment for whitening against hyper-pigmentation and sunburn because it lends itself to self-administration, patient compliance and an absence of systemic adverse effects. However, high-molecular-weight, hydrophilic chemicals are difficult to use as transdermal delivery drugs and the use of topical drugs has been highly limited. There are now many potent tyrosinase inhibitors, for example, sulfite or kojic acid, but the efficacy of their skin transduction remains a big problem. Furthermore, melanogenesis inhibitors from natural sources have great potential, as they are considered to be safe and largely free from adverse side effects. We applied 11-arginine (11R), a cell-membrane-permeable peptide, as a transdermal delivery system with a skin delivery enhancer, pyrenbutyrate. We performed intracellular screening for melanogenesis inhibitors with 11R fused with several kinds of tyrosinase inhibitory peptides from natural sources. Of 28 tyrosinase peptides, 13 melanin synthesis inhibitory peptides were selected. Peptide No. 10 found in gliadin protein, a wheat component, most strongly inhibited melanin production. This No. 10 peptide, of only 8 amino acids, fused to 11R showed no cytotoxicity and inhibited melanin synthesis as determined through melanin content measured using an absorption spectrometer and observation with a transmission electron microscope. Next, we transduced this 11R-No. 10 into skin with an 11R transdermal delivery system after previous treatment with pyrenbutyrate and performed daily repetitive topical application for two weeks against a UV-induced sun-tanning guinea pig model. We observed a whitening effect in a model skin sample by Masson-Fontana staining and the 11R-No. 10 peptide-applied area showed significant melanogenesis inhibition. These results show that 11R using a transdermal drug delivery system with melanogenesis inhibitory peptide is a very safe and promising method for applications from cosmetics to the pharmaceutical industry. (C) 2014 Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.biomaterials.2014.01.052

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  • The acceleration of boron neutron capture therapy using multi-linked mercaptoundecahydrododecaborate (BSH) fused cell-penetrating peptide 査読

    Hiroyuki Michiue, Yoshinori Sakurai, Natsuko Kondo, Mizuki Kitamatsu, Feng Bin, Kiichiro Nakajima, Yuki Hirota, Shinji Kawabata, Tei-ichi Nishiki, Iori Ohmori, Kazuhito Tomizawa, Shin-ichi Miyatake, Koji Ono, Hideki Matsui

    BIOMATERIALS   35 ( 10 )   3396 - 3405   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:ELSEVIER SCI LTD  

    New anti-cancer therapy with boron neutron capture therapy (BNCT) is based on the nuclear reaction of boron-10 with neutron irradiation. The median survival of BNCT patients with glioblastoma was almost twice as long as those receiving standard therapy in a Japanese BNCT clinical trial. In this clinical trial, two boron compounds, BPA (boronophenylalanine) and BSH (sodium borocaptate), were used for BNCT. BPA is taken up into cells through amino acid transporters that are expressed highly in almost all malignant cells, but BSH cannot pass through the cell membrane and remains outside the cell. We simulated the energy transfer against the nucleus at different locations of boron from outside the cell to the nuclear region with neutron irradiation and concluded that there was a marked difference between inside and outside the cell in boron localization. To overcome this disadvantage of BSH in BNCT, we used a cell-penetrating peptide system for transduction of BSH. CPP (cell-membrane penetrating peptide) is very common peptide domains that transduce many physiologically active substances into cells in vitro and in vivo. BSH-fused CPPs can penetrate the cell membrane and localize inside a cell. To increase the boron ratio in one BSH-peptide molecule, 8BSH fused to 11R with a dendritic lysine structure was synthesized and administrated to malignant glioma cells and a brain tumor mouse model. 8BSH-11R localized at the cell nucleus and showed a very high boron value in ICP results. With neutron irradiation, the 8BSH-11R administrated group showed a significant cancer killing effect compared to the 100 times higher concentration of BSH-administrated group. We concluded that BSH-fused CPPs were one of the most improved and potential boron compounds in the next-stage BNCT trial and 8BSH-11R may be applied in the clinical setting. (C) 2013 Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.biomaterials.2013.12.055

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  • Novel multi-linked mercaptoundecahydrododecaborate (BSH) fused cellpenetrating peptide accelerated boron neutron capture therapy (BNCT)

    H.Michiue, Y.Sakurai, N.Kondo, M.Kitamatsu, F.Bin, K.Nakajima, Y.Hirota, S.Kawabata, T.Nishiki, I.Ohmori, K.Tomizawa, S.Miyatake, K.Ono, H.Matsui

    Book of Abstracts for 16th International Congress on Neutron Capture Therapy, Cancer Society of Finland   187 - 188   2014年

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    記述言語:英語   掲載種別:研究論文(国際会議プロシーディングス)  

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  • Inhalation of 10% carbon dioxide rapidly terminates Scn1a mutation-related hyperthermia-induced seizures 査読

    Iori Ohmori, Keiichiro Hayashi, Haijiao Wang, Mamoru Ouchida, Naohiro Fujita, Takushi Inoue, Hiroyuki Michiue, Teiichi Nishiki, Hideki Matsui

    EPILEPSY RESEARCH   105 ( 1-2 )   220 - 224   2013年7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)   出版者・発行元:ELSEVIER SCIENCE BV  

    The aim of this study was to assess the anticonvulsant effect of carbon dioxide (CO2) on Scn1a mutation-related febrile seizures. We examined physiological changes in the blood gas levels after the induction of hyperthermia-induced seizures (HISs), which were associated with the Scn1a missense mutation. We determined the efficacy of inhalation of 5% or 10% CO2 to treat HISs. HISs were evoked in Scn1a mutant and wild-type (WT) rats by hot water baths. To determine the anticonvulsant effect of CO2 inhalation, rats were placed in a chamber filled with air or mixed gas containing 5% CO2 or 10% CO2 for 3 min, immediately after the induction of HISs. We also analyzed the blood gas levels at the end of inhalation of CO2. Hot water bathing induced a significant reduction in the partial pressure of CO2 (pCO(2)) and respiratory alkalosis in the WT and Scn1a mutant rats. HISs were evoked in 100% of the Scn1a mutant rats within 5 min, but in none of the WT rats. The Scn1a mutant rats demonstrated a higher HISs susceptibility associated with respiratory alkalosis than the WT rats. Inhalation of 10% CO2 shortened the seizure duration from 62.6 +/- 12.1 s to 15.5 +/- 1.0 s. Blood gas analysis after the inhalation of 10% CO2 demonstrated an elevated pCO(2) level and respiratory acidosis. Inhalation of 10% CO2 demonstrated a potent and fast-acting anticonvulsant effect against HISs. (C) 2013 Elsevier B.V. All rights reserved.

    添付ファイル: 2013 CO2 inhalation 95530ced1260ec360189758b7e073b2a.pdf

    DOI: 10.1016/j.eplepsyres.2013.01.003

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  • CACNA1A variants may modify the epileptic phenotype of Dravet syndrome 査読

    Iori Ohmori, Mamoru Ouchida, Katsuhiro Kobayashi, Yoshimi Jitsumori, Akiko Mori, Hiroyuki Michiue, Teiichi Nishiki, Yoko Ohtsuka, Hideki Matsui

    NEUROBIOLOGY OF DISEASE   50   209 - 217   2013年2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)   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    Dravet syndrome is an intractable epileptic syndrome beginning in the first year of life. De novo mutations of SCN1A, which encode the Na(v)1.1 neuronal voltage-gated sodium channel, are considered the major cause of Dravet syndrome. In this study, we investigated genetic modifiers of this syndrome.
    We performed a mutational analysis of all coding exons of CACNA1A in 48 subjects with Dravet syndrome. To assess the effects of CACNA1A variants on the epileptic phenotypes of Dravet syndrome, we compared clinical features in two genotype groups: 1) subjects harboring SCN1A mutations but no CACNA1A variants (n = 20) and 2) subjects with SCN1A mutations plus CACNA1A variants (n = 20). CACNA1A variants detected in patients were studied using heterologous expression of recombinant human Ca(v)2.1 in HEK 293 cells and whole-cell patch-clamp recording.
    Nine CACNA1A variants, including six novel ones, were detected in 21 of the 48 subjects (43.8%). Based on the incidence of variants in healthy controls, most of the variants seemed to be common polymorphisms. However, the subjects harboring SCN1A mutations and CACNA1A variants had absence seizures more frequently than the patients with only SCN1A mutations (8/20 vs. 0/20, p = 0.002). Moreover, the former group of subjects exhibited earlier onset of seizures and more frequent prolonged seizures before one year of age, compared to the latter group of subjects. The electrophysiological properties of four of the five novel Ca(v)2.1 variants exhibited biophysical changes consistent with gain-of-function. We conclude that CACNA1A variants in some persons with Dravet syndrome may modify the epileptic phenotypes. (C) 2012 Elsevier Inc. All rights reserved.

    添付ファイル: 2013 CACNA1A variants may modify the epileptic phenotype of Dravet syndrome.pdf

    DOI: 10.1016/j.nbd.2012.10.016

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  • High-frequency EEG oscillations in hyperthermia-induced seizures of Scn1a mutant rats 査読

    Katsuhiro Kobayashi, Iori Ohmori, Keiichiro Hayashi, Yuichiro Kitagawa, Mamoru Ouchida, Takushi Inoue, Yoko Ohtsuka

    EPILEPSY RESEARCH   103 ( 2-3 )   161 - 166   2013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:ELSEVIER SCIENCE BV  

    We examined high-frequency oscillations (HFOs) in the ictal cortical EEGs of hyperthermia-induced seizures in a rat model of febrile seizures with an SCN1A mutation as a means of investigating the pathophysiological mechanisms underlying the generation of febrile seizures. We used 13 male homozygous Scn1a-N1417H mutant rats (F344/NSlc-Scn1a(Kyo811)) and 10 wild-type control rats.
    Generalized tonic-clonic seizures were induced in all mutant rats, and HFOs with frequencies ranging from 200 to 400 Hz were found to precede spikes during the clonic phases of these seizures in the ictal EEGs. The proportion of all spikes in each seizure that were associated with HFOs increased with age. In time-frequency spectra of the EEG data, the HFOs had a mean peak frequency of 301.1 +/- 65.4 Hz (range: 156.3-468.8 Hz) and a mean peak power of 24.6 +/- 3.8 dB (range: 11.4-33.4 dB); the peak power increased with age. Regarding the wild-type rats, a brief seizure without unmistakable HFOs was exceptionally induced in only one rat.
    The generation mechanism of febrile seizures is still an unanswered question. The detection of HFOs from the ictal EEGs of hyperthermia-induced seizures may provide a cue to answering this open question, although in this research we were unable to provide sufficient evidence to prove that the generation of HFOs depended on the mutation. (C) 2012 Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.eplepsyres.2012.07.020

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  • Acute encephalopathy with a novel point mutation in the SCN2A gene 査読

    Katsuhiro Kobayashi, Hiroki Ohzono, Mayu Shinohara, Makiko Saitoh, Iori Ohmori, Yoko Ohtsuka, Masashi Mizuguchi

    EPILEPSY RESEARCH   102 ( 1-2 )   109 - 112   2012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 SCIENCE BV  

    Mutations of the neuronal voltage-gated sodium channel alpha subunit type II (SCN2A) cause various epileptic syndromes, but have never been reported in association with acute encephalopathy. To validate the involvement of SCN2A mutations in acute encephalopathy, we screened 25 patients and found a novel missense mutation (Met1128Thr) in a patient With acute encephalitis with refractory, repetitive partial seizures (AERRPS). This finding suggests that SCN2A mutation is a predisposing factor for acute encephalopathy. (C) 2012 Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.eplepsyres.2012.04.016

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  • Combining poly-arginine with the hydrophobic counter-anion 4-(1-pyrenyl)-butyric acid for protein transduction in transdermal delivery 査読

    Gerile Candan, Hiroyuki Michiue, Sanae Ishikawa, Atsushi Fujimura, Keiichiro Hayashi, Atsuhito Uneda, Akiko Mori, Iori Ohmori, Tei-ichi Nishiki, Hideki Matsui, Kazuhito Tomizawa

    BIOMATERIALS   33 ( 27 )   6468 - 6475   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:ELSEVIER SCI LTD  

    Topical therapy is the most favored form of treatment for whitening against hyperpigmentation and sunburn because it lends itself to self-administration, patient compliance, and absence of systemic adverse effects. However, transdermal delivery of hydrophilic chemicals is difficult. The main purpose of this study is to develop a delivering system of hydrophilic drugs and proteins across the skin. Hydroquinone (HQ), a well-known tyrosinase inhibitor and antimelanogenesis compound, and enhanced green fluorescent protein (EGFP) were fused with eleven poly-arginine (11R). Both HQ-11R and EGFP-11R were efficiently delivered in B16 cells, a mouse melanoma cell line. HQ-11R was as effective as HQ alone at inhibiting melanin synthesis in B16 cells. EGFP-11R was efficiently delivered into cells of the epidermis with 4-(1-pyrenyl)-butyric acid (PB), a counteranion bearing an aromatic hydrophobic moiety, in vivo, but EGFP alone or EGFP-11R without PB was not. Finally, topical application of HQ-11R with PB significantly inhibited UV irradiation-induced pigmentation in guinea pigs compared with HQ alone. These results suggest that topical therapy using poly-arginine in combination with PB is useful for the delivery of hydrophilic drugs and proteins by the transdermal route. (c) 2012 Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.biomaterials.2012.04.056

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  • A protein transduction method using oligo-arginine (3R) for the delivery of transcription factors into cell nuclei 査読

    Takashi Hitsuda, Hiroyuki Michiue, Mizuki Kitamatsu, Atsushi Fujimura, Feifei Wang, Takahiro Yamamoto, Xiao-Jian Han, Hiroshi Tazawa, Atsuhito Uneda, Iori Ohmori, Tei-ichi Nishiki, Kazuhito Tomizawa, Hideki Matsui

    BIOMATERIALS   33 ( 18 )   4665 - 4672   2012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 LTD  

    Protein transduction with cell-penetrating peptides such as poly-arginine and HIV TAT peptides is widely used to deliver proteins, peptides, siRNA and biologically active compounds. It has been thought that poly-arginine peptides transduce proteins in a manner dependent on the number of arginine residues and oligo-peptides such as three arginines (3R) are ineffective. Here we showed that 3R-fused proteins were effectively delivered and functioned in cells co-treated with pyrenebutyrate, a counteranion bearing an aromatic hydrophobic moiety. Little 3R was transduced in glioma cells without pyrenebutyrate whereas the oligo-arginine was effectively delivered with pyrenebutyrate. Enhanced green fluorescence protein (eGFP) fused with 3R was effectively delivered into various kinds of cells including primary cultured cells and suspended cells in the presence of pyrenebutyrate. p53 fused with 3R (3R-p53) was delivered into glioma cells without pyrenebutyrate but could not be translocated into the ncleus. In contrast, 3R-p53 was observed in nuclei of glioma cells when co-applied with pyrenebutyrate. Although 3R-p53 was delivered less effectively than 11R-p53 with pyrenebutyrate, its transcriptional activity was higher than that of 11R-p53. Moreover, a single administration of 3R-p53 with pyrenebutyrate significantly inhibited the growth of cancer cells. These results suggest protein transduction using an oligo-arginine (3R) with pyrenebutyrate to be a good tool for the delivery of functional transcription factors and a promising method of treating cancer. (C) 2012 Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.biomaterials.2012.02.049

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  • RGS2 mediates the anxiolytic effect of oxytocin 査読

    Naoki Okimoto, Oliver J. Bosch, David A. Slattery, Konstanze Pflaum, Hiroaki Matsushita, Fan-Yan Wei, Masayasu Ohmori, Tei-ichi Nishiki, Iori Ohmori, Yuji Hiramatsu, Hideki Matsui, Inga D. Neumann, Kazuhito Tomizawa

    BRAIN RESEARCH   1453   26 - 33   2012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:ELSEVIER SCIENCE BV  

    The neuropeptide oxytocin (OT) has been shown to exert multiple functions in both males and females, and to play a key role in the regulation of emotionality in the central nervous system (CNS). OT has an anxiolytic effect in the CNS of rodents and humans. However, the molecular mechanisms of this effect are unclear. Here we show that OT induced the expression of regulator of G-protein signaling 2 (RGS2), a regulatory factor for anxiety, in the central amygdala (CeA) of female mice. Bath application of OT increased RGS2 levels in slices of the amygdala of virgin mice. RGS2 levels in the CeA were higher in lactating mice than in virgin mice. In contrast, RGS2 levels in mice that had given birth did not increase when the pups were removed. Acute restraint stress for 4 h induced RGS2 expression within the CeA, and local administration of an OT receptor antagonist inhibited this expression. Behavioral experiments revealed that transient restraint stress had an anxiolytic effect in wild-type females, and RGS2 levels in the CeA correlated with the anxiolytic behavior. By contrast, in the OT receptor-deficient mice, restraint stress neither increased RGS2 levels in the CeA nor had an anxiolytic effect. These results suggest that OT displays an anxiolytic effect through the induction of RGS2 expression in the CNS. (C) 2012 Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.brainres.2012.03.012

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  • Additional information regarding "Dravet syndrome: Inroads into understanding epileptic encephalopathies" 査読

    Katsuhiro Kobayashi, Yoko Ohtsuka, Iori Ohmori

    JOURNAL OF PEDIATRICS   160 ( 3 )   532 - 533   2012年3月

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    担当区分:最終著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:MOSBY-ELSEVIER  

    DOI: 10.1016/j.jpeds.2011.11.058

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  • Ca2+-independent syntaxin binding to the C2B effector region of synaptotagmin 査読

    Toshio Masumoto, Koichiro Suzuki, Iori Ohmori, Hiroyuki Michiue, Kazuhito Tomizawa, Atsushi Fujimura, Tei-ichi Nishiki, Hideki Matsui

    MOLECULAR AND CELLULAR NEUROSCIENCE   49 ( 1 )   1 - 8   2012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  

    Although synaptotagmin I, which is a calcium (Ca2+)-binding synaptic vesicle protein, may trigger soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE)-mediated synaptic vesicle exocytosis, the mechanisms underlying the interaction between these proteins remain controversial, especially with respect to the identity of the protein(s) in the SNARE complex that bind(s) to synaptotagmin and whether Ca2+ is required for their highly effective binding. To address these questions, native proteins were solubilized, immunoprecipitated from rat brain extracts, and analyzed by immunoblotting. SNARE complexes comprising syntaxin 1, 25-kDa synaptosomal-associated protein (SNAP-25), and synaptobrevin 2 were coprecipitzted with synaptotagmin I in the presence of ethylene glycol tetraacetic acid. The amount of cop recipitated proteins was significantly unaltered by the addition of Ca2+ to the brain extract. To identify the component of the SNARE complex that bound to synaptotagmin, SNARE was coexpressed with synaptotagmin in HEK293 cells and immunoprecipitated. Syntaxin, but not SNAP-25 and synaptobrevin, bound to synaptotagmin in a Ca2+-independent manner, and the binding was abolished in the presence of 1 M NaCl. Synaptotagmin contains 2 Ca2+-binding domains (C(2)A, C2B). Mutating the positively charged lysine residues in the putative effector-binding region of the C2B domain, which are critical for transmitter release, markedly inhibited synaptotagmin-syntaxin binding, while similar mutations in the C(2)A domain had no effect on binding. Synaptotagmin-syntaxin binding was reduced by mutating multiple negatively charged glutamate residues in the amino-terminal half of the syntaxin SNARE motif. These results indicate that synaptotagmin I binds to syntaxin 1 electrostatically through its C2B domain effector region in a Ca2+-independent fashion, providing biochemical evidence that synaptotagmin I binds SNARE complexes before Ca2+ influx into presynaptic nerve terminals. (C) 2011 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.mcn.2011.09.007

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  • Acute encephalopathy in children with Dravet syndrome 査読

    Akihisa Okumura, Mitsugu Uematsu, George Imataka, Manabu Tanaka, Tohru Okanishi, Tetsuo Kubota, Akira Sudo, Jun Tohyama, Megumi Tsuji, Iori Ohmori, Misako Naiki, Ayako Hiraiwa-Sofue, Hitoshi Sato, Shinji Saitoh, Toshiaki Shimizu

    EPILEPSIA   53 ( 1 )   79 - 86   2012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:WILEY-BLACKWELL  

    Purpose: The occurrence of acute encephalopathy in children with Dravet syndrome has been reported sporadically. This study clarified the features of acute encephalopathy in children with Dravet syndrome.
    Methods: Through the mailing list of the Annual Zao Conference on Pediatric Neurology, we collected 15 patients with clinically diagnosed Dravet syndrome, who had acute encephalopathy, defined as a condition with decreased consciousness with or without other neurologic symptoms, such as seizures, lasting for &gt; 24 h in association with infectious symptoms. Key
    Findings: There were seven boys and eight girls. A mutation of the SCN1A gene was present in nine (truncation in six and missense in three). The frequency of seizures during the 3 months before the onset of acute encephalopathy was monthly in seven children and none in three. The median age at the onset of acute encephalopathy was 44 months ( range 8-184 months). All children had status epilepticus followed by coma as the initial manifestation. Two different distributions of brain lesions were observed on diffusion-weighted images during the acute phase: cerebral cortex-dominant lesions with or without deep gray matter involvement and subcortical- dominant lesions. Four children died; nine survived with severe sequelae, and two had moderate sequelae.
    Significance: We must be aware that acute encephalopathy is an important complication in children with Dravet syndrome, and associated with fulminant clinical manifestations and a poor outcome.

    DOI: 10.1111/j.1528-1167.2011.03311.x

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  • ANTIDEPRESSANT-LIKE EFFECT OF SILDENAFIL THROUGH OXYTOCIN-DEPENDENT CYCLIC AMP RESPONSE ELEMENT-BINDING PROTEIN PHOSPHORYLATION 査読

    H. Matsushita, M. Matsuzaki, X-J. Han, T. -I. Nishiki, I. Ohmori, H. Michiue, H. Matsui, K. Tomizawa

    NEUROSCIENCE   200   13 - 18   2012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:PERGAMON-ELSEVIER SCIENCE LTD  

    Oxytocin (OT) levels in plasma increase during sexual response and are significantly lower in patients with depression. A drug for the treatment of sexual dysfunction, sildenafil, enhances the electrically evoked release of OT from the posterior pituitary. In this study, we showed that sildenafil had an antidepressant-like effect through activation of an OT signaling pathway. Application of sildenafil reduced depression-related behavior in male mice. The antidepressant-like effect was blocked by an OT receptor (OTR) antagonist and was absent in OTR knockout (KO) mice. Sildenafil increased the phosphorylation of cAMP response element-binding protein (CREB) in the hippocampus. The OTR antagonist inhibited sildenafil-induced CREB phosphorylation and sildenafil had no effect on CREB phosphorylation in OTR KO mice. These results suggest sildenafil to have an antidepressant-like effect through the activation of OT signaling and to be a promising drug for the treatment of depression. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.neuroscience.2011.11.001

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  • Scn1a遺伝子変異ラットを用いた抗てんかん薬の熱性けいれん抑制効果

    林桂一郎, 大守伊織, 松井秀樹

    岡山医学会雑誌   1308   115 - 117   2012年

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.4044/joma.124.115

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  • Dravet syndrome with an exceptionally good seizure outcome in two adolescents 査読

    Katsuhiro Kobayashi, Iori Ohmori, Mamoru Ouchida, Yoko Ohtsuka

    EPILEPTIC DISORDERS   13 ( 3 )   340 - 344   2011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:JOHN LIBBEY EUROTEXT LTD  

    We present two children who exhibited the characteristics of Dravet syndrome during infancy and young childhood, with SCN1A mutation, but nevertheless achieved seizure freedom for at least four years during adolescence. These patients had no episodes of convulsive status epilepticus with a duration of more than 30 minutes and their overall favourable seizure outcome may be related to the prevention of convulsive status epilepticus.

    DOI: 10.1684/epd.2011.0453

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  • Therapy for hyperthermia-induced seizures in Scn1a mutant rats 査読

    Keiichiro Hayashi, Satoshi Ueshima, Mamoru Ouchida, Tomoji Mashimo, Teiichi Nishiki, Toshiaki Sendo, Tadao Serikawa, Hideki Matsui, Iori Ohmori

    EPILEPSIA   52 ( 5 )   1010 - 1017   2011年5月

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    担当区分:最終著者, 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:WILEY-BLACKWELL  

    Purpose: Mutations in the SCN1A gene, which encodes the alpha 1 subunit of voltage-gated sodium channels, cause generalized epilepsy with febrile seizures plus (GEFS+) and severe myoclonic epilepsy of infancy (SMEI). N1417H-Scn1a mutant rats are considered to be an animal model of human FS+ or GEFS+. To assess the pharmacologic validity of this model, we compared the efficacies of eight different antiepileptic drugs (AEDs) for the treatment of hyperthermia-induced seizures using N1417H-Scn1a mutant rats.
    Methods: AEDs used in this study included valproate, carbamazepine (CBZ), phenobarbital, gabapentin, acetazolamide, diazepam (DZP), topiramate, and potassium bromide (KBr). The effects of these AEDs were evaluated using the hot water model, which is a model of experimental FS. Five-week-old rats were pretreated with each AED and immersed in water at 45 degrees C to induce hyperthermia-induced seizures. The seizure manifestations and video-electroencephalographic recordings were evaluated. Furthermore, the effects of each AED on motor coordination and balance were assessed using the balance-beam test.
    Key Findings: KBr significantly reduced seizure durations, and its anticonvulsant effects were comparable to those of DZP. On the other hand, CBZ decreased the seizure threshold. In addition, DZP and not KBr showed significant impairment in motor coordination and balance.
    Significance: DZP and KBr showed potent inhibitory effects against hyperthermia-induced seizures in the Scn1a mutant rats, whereas CBZ exhibited adverse effects. These responses to hyperthermia-induced seizures were similar to those in patients with GEFS+ and SMEI. N1417H-Scn1a mutant rats may, therefore, be useful for testing the efficacy of new AEDs against FS in GEFS+ and SMEI patients.

    DOI: 10.1111/j.1528-1167.2011.03046.x

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  • Expression of a Constitutively Active Calcineurin Encoded by an Intron-Retaining mRNA in Follicular Keratinocytes 査読

    Atsushi Fujimura, Hiroyuki Michiue, Tei-ichi Nishiki, Iori Ohmori, Fan-Yan Wei, Hideki Matsui, Kazuhito Tomizawa

    PLOS ONE   6 ( 3 )   e17685   2011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:PUBLIC LIBRARY SCIENCE  

    Hair growth is a highly regulated cyclical process. Immunosuppressive immunophilin ligands such as cyclosporin A (CsA) and FK506 are known as potent hair growth modulatory agents in rodents and humans that induce active hair growth and inhibit hair follicle regression. The immunosuppressive effectiveness of these drugs has been generally attributed to inhibition of T cell activation through well-characterized pathways. Specifically, CsA and FK506 bind to intracellular proteins, principally cyclophilin A and FKBP12, respectively, and thereby inhibit the phosphatase calcineurin (Cn). The calcineurin (Cn)/NFAT pathway has an important, but poorly understood, role in the regulation of hair follicle development. Here we show that a novel-splicing variant of calcineurin A beta CnA beta-FK, which is encoded by an intron-retaining mRNA and is deficient in the autoinhibitory domain, is predominantly expressed in mature follicular keratinocytes but not in the proliferating keratinocytes of rodents. CnA beta-FK was weakly sensitive to Ca(2+) and dephosphorylated NFATc2 under low Ca(2+) levels in keratinocytes. Inhibition of Cn/NFAT induced hair growth in nude mice. Cyclin G2 was identified as a novel target of the Cn/NFATc2 pathway and its expression in follicular keratinocytes was reduced by inhibition of Cn/NFAT. Overexpression of cyclin G2 arrested the cell cycle in follicular keratinocytes in vitro and the Cn inhibitor, cyclosporin A, inhibited nuclear localization of NFATc2, resulting in decreased cyclin G2 expression in follicular keratinocytes of rats in vivo. We therefore suggest that the calcineurin/NFAT pathway has a unique regulatory role in hair follicle development.

    DOI: 10.1371/journal.pone.0017685

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  • Regulation of Mitochondrial Dynamics and Neurodegenerative Diseases 査読

    Xiao-Jian Han, Kazuhito Tomizawa, Atsushi Fujimura, Iori Ohmori, Tei-ichi Nishiki, Masayuki Matsushita, Hideki Matsui

    ACTA MEDICA OKAYAMA   65 ( 1 )   1 - 10   2011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:OKAYAMA UNIV MED SCHOOL  

    Mitochondria are important cellular organelles in most metabolic processes and have a highly dynamic nature, undergoing frequent fission and fusion. The dynamic balance between fission and fusion plays critical roles in mitochondrial functions. In recent studies, several large GTPases have been identified as key molecular factors in mitochondrial fission and fusion. Moreover, the posttranslational modifications of these large GTPases, including phosphorylation, ubiquitination and SUMOylation, have been shown to be involved in the regulation of mitochondrial dynamics. Neurons are particularly sensitive and vulnerable to any abnormalities in mitochondrial dynamics, due to their large energy demand and long extended processes. Emerging evidences have thus indicated a strong linkage between mitochondria and neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease and Huntington's disease. In this review, we will describe the regulation of mitochondrial dynamics and its role in neurodegenerative diseases.

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  • Oxytocin mediates the antidepressant effects of mating behavior in male mice 査読

    Hiroaki Matsushita, Kazuhito Tomizawa, Naoki Okimoto, Tei-ichi Nishiki, Iori Ohmori, Hideki Matsui

    NEUROSCIENCE RESEARCH   68 ( 2 )   151 - 153   2010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 IRELAND LTD  

    A significant association between plasma oxytocin (OT) levels and depression has been demonstrated. A recent study found that sexual activity and mating with a female induced the release of OT in the central nervous system of male rats. Here we examined the effect of mating behavior on depression-related behavior in wild-type (WT) and OT receptor-deficient (OTR KO) male mice. The WT males showed a reduction in depression-related behavior after mating behavior, but the OTR KO mice did not. Application of an OTR antagonist inhibited mating behavior-induced antidepressant effect in WT males. OT may mediate the antidepressant effects of mating behavior. (C) 2010 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

    DOI: 10.1016/j.neures.2010.06.007

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  • Genetic seizure susceptibility underlying acute encephalopathies in childhood 査読

    Katsuhiro Kobayashi, Mamoru Ouchida, Akihisa Okumura, Yoshihiro Maegaki, Itsuko Nishiyama, Hideki Matsui, Yoko Ohtsuka, Iori Ohmori

    EPILEPSY RESEARCH   91 ( 2-3 )   143 - 152   2010年10月

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    担当区分:最終著者   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  

    We herein investigated risk factors of pediatric acute encephalopathy (AE) regarding the hitherto uncharacterized genetic background of seizure susceptibility underlying the pathogenesis of AE. The study included 15 patients with a history of various types of AE in childhood. We undertook the mutational analysis of the neuronal sodium channel alpha 1 subunit (SCN1A) gene which is the most representative gene for hyperthermia-induced seizure susceptibility.
    Six patients (40%) had a positive family history of seizures or AE, especially febrile seizures, in first- or second-degree relatives. The SCN1A-R1575C mutation was detected in a patient with a history of acute encephalitis with refractory, repetitive partial seizures (AERRPS) and also in the patient&apos;s apparently healthy father.
    In the present study, dense familial seizure predisposition was present in the patients with AE. Although the presence of seizure susceptibility alone is insufficient to cause AE, it can exacerbate seizures and the subsequent development of inflammatory reactions in the brain when environmental factors are included. Genetic seizure susceptibility may contribute to some types of AE in childhood. Crown Copyright (C) 2010 Published by Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.eplepsyres.2010.07.005

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  • Nationwide survey (incidence, clinical course, prognosis) of Rasmussen’s encephalitis. 査読

    Muto A, Oguni H, Takahashi Y, Shirasaka Y, Sawaishi Y, Yano T, Hoshida T, Osaka H, Nakasu S, Akasaka N, Sugai K, Miyamoto A, Takahashi S, Suzuki M, Ohmori I, Nabatame S, Osawa M

    Brain Dev   32 ( 6 )   445 - 453   2010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)  

    DOI: 10.1016/j.braindev.2009.10.004

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  • A Missense Mutation of the Gene Encoding Voltage-Dependent Sodium Channel (Na(v)1.1) Confers Susceptibility to Febrile Seizures in Rats 査読

    Tomoji Mashimo, Iori Ohmori, Mamoru Ouchida, Yukihiro Ohno, Toshiko Tsurumi, Takafumi Miki, Minoru Wakamori, Shizuka Ishihara, Takashi Yoshida, Akiko Takizawa, Megumi Kato, Masumi Hirabayashi, Masashi Sasa, Yasuo Mori, Tadao Serikawa

    JOURNAL OF NEUROSCIENCE   30 ( 16 )   5744 - 5753   2010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:SOC NEUROSCIENCE  

    Although febrile seizures (FSs) are the most common convulsive syndrome in infants and childhood, the etiology of FSs has remained unclarified. Several missense mutations of the Na(v)1.1 channel (SCN1A), which alter channel properties, have been reported in a familial syndrome of GEFS+ (generalized epilepsy with febrile seizures plus). Here, we generated Scn1a-targeted rats carrying a missense mutation (N1417H) in the third pore region of the sodium channel by gene-driven ENU (N-ethyl-N-nitrosourea) mutagenesis. Despite their normal appearance under ordinary circumstances, Scn1a mutant rats exhibited remarkably high susceptibility to hyperthermia-induced seizures, which involve generalized clonic and/or tonic-clonic convulsions with paroxysmal epileptiform discharges. Whole-cell patch-clamp recordings from HEK cells expressing N1417H mutant channels and from hippocampal GABAergic interneurons of N1417H mutant rats revealed a significant shift of the inactivation curve in the hyperpolarizing direction. In addition, clamp recordings clearly showed the reduction in action potential amplitude in the hippocampal interneurons of these rats. These findings suggest that a missense mutation (N1417H) of the Na(v)1.1 channel confers susceptibility to FS and the impaired biophysical properties of inhibitory GABAergic neurons underlie one of the mechanisms of FS.

    DOI: 10.1523/JNEUROSCI.3360-09.2010

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  • てんかん関連変異型ナトリウムチャネルNav1.1に対する抗てんかん薬の薬理効果

    大守伊織, 林桂一郎

    てんかん治療研究振興財団研究年報   21   43 - 48   2010年

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    担当区分:筆頭著者, 責任著者   記述言語:日本語   掲載種別:研究論文(研究会,シンポジウム資料等)  

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  • Hyperthermia-induced seizure-susceptible rats: a novel model of febrile seizures

    Tomoji Mashimo, Iori Ohmori, Mamoru Ouchida, Yukihiro Ohno, Toshiko Tsurumi, Takafumi Miki, Minoru Wakamori, Yasuo Mori, Tadao Serikawa

    NEUROSCIENCE RESEARCH   65   S47 - S47   2009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:ELSEVIER IRELAND LTD  

    DOI: 10.1016/j.neures.2009.09.084

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  • Ca(v)2.1 DYSFUNCTION MAY BE A GENETIC MODIFIER OF SEVERE MYOCLONIC EPILEPSY IN INFANCY

    Iori Ohmori, Mamoru Ouchida, Takafumi Miki, Nobuyoshi Mimaki, Shigeki Kiyonaka, Teiichi Nishiki, Kazuhito Tomizawa, Yasuo Mori, Hideki Matsui

    JOURNAL OF PHYSIOLOGICAL SCIENCES   59   515 - 515   2009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:SPRINGER TOKYO  

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  • A CACNB4 mutation shows that altered Ca(v)2.1 function may be a genetic modifier of severe myoclonic epilepsy in infancy 査読

    Iori Ohmori, Mamoru Ouchida, Takafumi Miki, Nobuyoshi Mimaki, Shigeki Kiyonaka, Teiichi Nishiki, Kazuhito Tomizawa, Yasuo Mori, Hideki Matsui

    NEUROBIOLOGY OF DISEASE   32 ( 3 )   349 - 354   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:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    Mutations of SCN1A, encoding the voltage-gated sodium channel alpha l subunit, represent the most frequent genetic cause of severe myoclonic epilepsy in infancy (SMEI). The purpose of this study was to determine if mutations in other seizure susceptibility genes are also present and could modify the disease severity. All coding exons of SCN1B, GABRG2, and CACNB4 genes were screened for mutations in 38 SCN1A-mutation-positive SMEI probands. We identified one proband who was heterozygous for a de novo SCN1A nonsense mutation (R568X) and another missense mutation (R468Q) of the CACNB4 gene. The latter mutation was inherited from his father who had a history of febrile seizures. An electrophysiological analysis of heterologous expression system exhibited that R468Q-CACNB4 showed greater Ba(2+) current density compared with the wild-type CACNB4. The greater Ca(v)2.1 currents caused by the R468Q-CACNB4 mutation may increase the neurotransmitter release in the excitatory neurons under the condition of insufficient inhibitory neurons caused primarily by the SCN1A mutation. (C) 2008 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.nbd.2008.07.017

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  • A screening test for the prediction of Dravet syndrome before one year of age 査読

    Junri Hattori, Mamoru Ouchida, Junko Ono, Susumu Miyake, Satoshi Maniwa, Nobuyoshi Mimaki, Yoko Ohtsuka, Iori Ohmori

    EPILEPSIA   49 ( 4 )   626 - 633   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:WILEY  

    Purpose: Our aim was to develop a screening test to predict Dravet syndrome before the first birthday based on the clinical characteristics of infants and the SCN1A mutation analysis.
    Methods: Ninety-six patients who experienced febrile seizures before the age of one were enrolled. The patients were divided into two groups-the Dravet syndrome group (n = 46) and the non-Dravet syndrome group (n = 50). We compared the clinical characteristics before one year of age of the two groups. We analyzed all coding exons of the SCN1A gene by the direct sequencing method. Scores from 0 to 3 were assigned to each risk factor based on the odds ratio and p-value.
    Results: An age of onset of febrile seizure &lt;= 7 months, a total number of seizures &gt;= 5, and prolonged seizures lasting more than 10 min. were regarded as significant risk factors for Dravet syndrome. Other factors highly predictive of this syndrome were hemiconvulsions, partial seizures, myoclonic seizures, and hot water-induced seizures. A total clinical score of six or above was the cutoff value indicating a high risk of Dravet syndrome. SCN1A missense and truncated mutations were detected significantly more often in the Dravet syndrome group than in the non-Dravet syndrome group.
    Discussion: This simple screening test was designed to be used by general pediatricians. It could help to predict Dravet syndrome before one year of age. If the sum of the clinical risk score is &gt;= 6, then the performance of an SCN1A mutation analysis is recommended.

    DOI: 10.1111/j.1528-1167.2007.01475.x

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  • Rasmussen encephalitis associated with SCN1A mutation 査読

    Iori Ohmori, Mamoru Ouchida, Katsuhiro Kobayashi, Yoshimi Jitsumori, Takushi Inoue, Kenji Shimizu, Hideki Matsui, Yoko Ohtsuka, Yoshihiro Maegaki

    EPILEPSIA   49 ( 3 )   521 - 526   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:BLACKWELL PUBLISHING  

    Mutations in the SCN1A gene, encoding the neuronal voltage-gated sodium channel alpha 1 subunit, cause SMEI, GEFS+, and related epileptic syndromes. We herein report the R1575C-SCN1A mutation identified in a patient with Rasmussen encephalitis. R1575C were constructed in a recombinant human SCN1A and then heterologously expressed in HEK293 cells along with the human beta 1 and beta 2 sodium channel accessory subunits. Whole-cell patch-clamp recording was used to define biophysical properties. The R1575C channels exhibited increased channel availability and an increased persistent sodium current in comparison to the wild-type. These defects of electrophysiological properties can result in neuronal hyperexitability. The seizure susceptibility allele may influence the pathogenesis of Rasmussen encephalitis in this case.

    DOI: 10.1111/j.1528-1167.2007.01411.x

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  • Development of bionanocapsules targeting brain tumors 査読

    Yumi Tsutsui, Kazuhito Tomizawa, Mana Nagita, Hiroyuki Michiue, Tei-ichi Nishiki, Iori Ohmori, Masaharu Seno, Hideki Matsui

    JOURNAL OF CONTROLLED RELEASE   122 ( 2 )   159 - 164   2007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  

    Bionanocapsules (BNCs) are hollow nanoparticles that are composed of L protein (the hepatitis B virus surface antigen) and show specific affinity for human hepatocytes. The pre-S1 peptide displayed on the surface of BNCs is the specific ligand for binding to the receptor on human hepatocytes. Therefore, BNCs are not delivered to other tissues, such as the brain. The aim of the present study was to develop a novel drug delivery system (DIDS) targeting brain tumors using BNCs that selectively targeted brain tumors. Epidermal growth factor receptor (EGFR), especially a constitutively active genomic sequence deletion variant of EGFR (EGFRvIII), is overexpressed in human glioblastoma. In the present study, we replaced the pre-S1 peptide with the antibody affinity motif of protein A and made hybrid BNCs conjugated with anti-human EGFR antibody recognizing EGFRvIII. The hybrid BNCs were efficiently delivered to glioma cells but not normal glial cells. Moreover, we confirmed the specific delivery of the hybrid BNCs to brain tumors in an in vivo brain tumor model. These results suggest that this new approach using BNCs is a promising system for brain tumor-targeted drug delivery. (C) 2007 Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.jconrel.2007.06.019

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  • A Cdk5 inhibitor enhances the induction of insulin secretion by exendin-4 both in vitro and in vivo 査読

    Kohsuke Kitani, Shigeo Oguma, Tei-Ichi Nishiki, Iori Ohmori, Herve Galons, Hideki Matsui, Laurent Meijer, Kazuhito Tomizawa

    JOURNAL OF PHYSIOLOGICAL SCIENCES   57 ( 4 )   235 - 239   2007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:PHYSIOLOGICAL SOC JAPAN  

    Exendin-4 (Ex4) is a peptide found in the lizard Heloderma suspectum, and it has a high similarity to glucagon-like peptide 1 (GLP-1). It induces insulin secretion without the risk of hypoglycemic episodes. Cyclin-dependent kinase 5 (Cdk5) is a serine/threonine kinase that is predominantly expressed in neurons. Recent studies have shown that this kinase regulates glucose-stimulated insulin secretion. Cdk5 inhibition enhances insulin secretion under conditions of stimulation by high glucose, but not low glucose. In the present study, we examined whether R-roscovitine (R-ros), a Cdk5 inhibitor, enhances insulin secretion induced by Ex4. R-ros induced Ex4-dependent insulin secretion under conditions of high glucose, but not low glucose in MIN6B1 cells. The enhancement by R-ros was also observed in db/db mice, a mouse model of type 2 diabetes. Moreover, long-term treatment with Ex4 and R-ros significantly improved HbA1c compared with treatment using only Ex4. These results suggest that a co-application of R-ros and Ex4 may become a promising therapy for the treatment of type 2 diabetes.

    DOI: 10.2170/physiolsci.RP006607

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  • Truncations of amphiphysin I by calpain inhibit vesicle endocytosis during neural hyperexcitation 査読

    Yumei Wu, Shuang Liang, Yoshiya Oda, Iori Ohmori, Tei-Ichi Nishiki, Kohji Takei, Hideki Matsui, Kazuhito Tomizawa

    EMBO JOURNAL   26 ( 12 )   2981 - 2990   2007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:NATURE PUBLISHING GROUP  

    Under normal physiological conditions, synaptic vesicle endocytosis is regulated by phosphorylation and Ca2+-dependent dephosphorylation of endocytic proteins such as amphiphysin and dynamin. To investigate the regulatory mechanisms that may occur under the conditions of excessive presynaptic Ca2+ influx observed preceding neural hyperexcitation, we examined hippocampal slices following high-potassium or high-frequency electrical stimulation (HFS). In both cases, three truncated forms of amphiphysin I resulted from cleavage by the protease calpain. In vitro, the binding of truncated amphiphysin I to dynamin I and copolymerization into rings with dynamin I were inhibited, but its interaction with liposomes was not affected. Moreover, overexpression of the truncated form of amphiphysin I inhibited endocytosis of transferrin and synaptic vesicles. Inhibiting calpain prevented HFS-induced depression of presynaptic transmission. Finally, calpain-dependent amphiphysin I cleavage attenuated kainate-induced seizures. These results suggest that calpain-dependent cleavage of amphiphysin I inhibits synaptic vesicle endocytosis during neural hyperexcitation and demonstrate a novel post-translational regulation of endocytosis.

    DOI: 10.1038/sj.emboj.7601741

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  • Nonfunctional SCN1A is common in severe myoclonic epilepsy of infancy 査読

    Iori Ohmori, Kristopher M. Kahlig, Thomas H. Rhodes, Dao W. Wang, Alfred L. George

    EPILEPSIA   47 ( 10 )   1636 - 1642   2006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:BLACKWELL PUBLISHING  

    Purpose: Mutations in SCN1A, encoding the human Na(V)1.1 neuronal voltage-gated sodium channel, cause the syndrome of severe myoclonic epilepsy of infancy (SMEI). Most SMEI-associated mutations are predicted to truncate the SCN1A protein, likely causing a loss of sodium channel function. However, many missense or in-frame deletion SCN1A mutations have also been reported in this disorder, but their functional impact is largely unknown. Here we report the functional characterization of eight SCN1A mutations (G177E, I227S, R393H, Y426N, H939Q, C959R, delF1289, and T1909I) previously identified in SMEI probands.
    Methods: SCN1A mutants were constructed in a recombinant human SCN1A and then heterologously expressed in human tsA201 cells along with the human beta(1) and beta(2) sodium channel accessory subunits. Whole-cell patch-clamp recording was used to define biophysical properties of each mutant and for comparison with the wild-type (WT) channel.
    Results: Six of the mutants were nonfunctional, but Y426N and T1909I generated measurable sodium channel activity. Cells expressing Y426N and T1909I had significantly lower current densities compared with WT-SCN1A. In addition, other biophysical abnormalities were observed for the two functional mutants including decreased channel availability (Y426N) and increased persistent sodium current (T1909I).
    Conclusions: We conclude that SMEI is caused either by complete loss of SCN1A function, or by dysfunctional sodium channels exhibiting mixed biophysical properties. This wide spectrum of functional defects observed among SCN1A mutations suggests that SMEI may result from more than a single molecular or cellular mechanism, or require other factors for pathogenesis.

    DOI: 10.1111/j.1528-1167.2006.00643.x

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  • Sodium channel dysfunction in intractable childhood epilepsy with generalized tonic-clonic seizures 査読

    TH Rhodes, CG Vanoye, Ohmori, I, Ogiwara, I, K Yamakawa, AL George

    JOURNAL OF PHYSIOLOGY-LONDON   569 ( 2 )   433 - 445   2005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:BLACKWELL PUBLISHING  

    Mutations in SCN1A, the gene encoding the brain voltage-gated sodium channel alpha(1) subunit (Na(V)1.1), are associated with genetic forms of epilepsy, including generalized epilepsy with febrile seizures plus (GEFS+ type 2), severe myoclonic epilepsy of infancy (SMEI) and related conditions. Several missense SCN1A mutations have been identified in probands affected by the syndrome of intractable childhood epilepsy with generalized tonic-clonic seizures (ICEGTC), which bears similarity to SMEI. To test whether ICEGTC arises from molecular mechanisms similar to those involved in SMEI, we characterized eight ICEGTC missense mutations by whole-cell patch clamp recording of recombinant human SCN1A heterologously expressed in cultured mammalian cells. Two mutations (G979R and T1709I) were non-functional. The remaining alleles (T808S, V983A, N1011I, V1611F, P1632S and F1808L) exhibited measurable sodium current, but had heterogeneous biophysical phenotypes. Mutant channels exhibited lower (V983A, N1011I and F1808L), greater (T808S) or similar (V1611F and P1632S) peak sodium current densities compared with wild-type (WT) SCN1A. Three mutations (V1611F, P1632S and F1808L) displayed hyperpolarized conductance-voltage relationships, while V983A exhibited a strong depolarizing shift in the voltage dependence of activation. All mutants except T808S had hyperpolarized shifts in the voltage dependence of steady-state channel availability. Three mutants (V1611F, P1632S and F1808L) exhibited persistent sodium current ranging from similar to 1-3% of peak current amplitude that was significantly greater than WT-SCN1A. Several mutants had impaired slow inactivation, with V983A showing the most prominent effect. Finally, all of the functional alleles exhibited reduced use-dependent channel inhibition. In summary, SCN1A mutations associated with ICEGTC result in a wide spectrum of biophysical defects, including mild-to-moderate gating impairments, shifted voltage dependence and reduced use dependence. The constellation of biophysical abnormalities for some mutants is distinct from those previously observed for GEFS+ and SMEI, suggesting possible, but complex, genotype-phenotype correlations.

    DOI: 10.1113/jphysiol.2005.094326

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  • Mutation screen of GABRA1, GABRB2 and GABRG2 genes in Japanese patients with absence seizures 査読

    M Ito, Ohmori, I, T Nakahori, M Ouchida, Y Ohtsuka

    NEUROSCIENCE LETTERS   383 ( 3 )   220 - 224   2005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 IRELAND LTD  

    Absence seizures are classified into typical and atypical absences according to clinical and EEG characteristics. Although missense mutations in the GABA(A) receptor gamma 2 subunits (GABRG2) gene have recently been detected in two families with typical absence seizures, no study has been carried out to clarify the relationship between atypical absence and GABA(A) receptors. We performed mutation analysis of all the coding exons of GABA(A) receptor alpha 1, beta 2 and gamma 2 subunit (GABRA1, GABRB2 and GABRG2) genes by direct sequencing to clarify whether there was common molecular biological mechanism underlying both typical and atypical absences. We recruited 52 unrelated Japanese patients, thirty-eight with typical absences and 14 with atypical absences. They consisted of 38 with childhood absence epilepsy, three with Lennox-Gastaut syndrome, two with epilepsy with myoclonic-astatic seizures and nine with epilepsy with continuous spike-waves during slow wave sleep. All of the subjects were idiopathic or cryptogenic cases without any organic brain lesions or underlying diseases. We detected five polymorphisms (T156C in GABRA1, C1194T in GABRB2, and C315T, T588C and C1230T in GABRG2), and they are silent mutations. In conclusion, mutations in GABRA1, GABRB2 and GABRG2 do not seem to be a major genetic cause of epilepsy with typical and atypical absences in Japanese subjects. (c) 2005 Elsevier Ireland Ltd. All fights reserved.

    DOI: 10.1016/j.neulet.2005.04.017

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  • Methyl-CpG binding protein 2 gene (MECP2) variations in Japanese patients with Rett syndrome: pathological mutations and polymorphisms 査読

    T Fukuda, Y Yamashita, S Nagamitsu, K Miyamoto, JJ Jin, I Ohmori, Y Ohtsuka, K Kuwajima, S Endo, T Iwai, H Yamagata, Y Tabara, T Miki, T Matsuishi, Kondo, I

    BRAIN & DEVELOPMENT   27 ( 3 )   211 - 217   2005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 SCIENCE BV  

    A total of 45 different mutations of methyl-CpG-binding protein 2 gene (MECP2) were identified in 145 of 219 Japanese patients with typical or atypical Rett syndrome (RTT) (66.2%). A missense mutation, T158M was the most common mutation of MECP2, identified in 22 (19.1%) patients, followed by four nonsense mutations, R168X (14.8%), R270X (13.0%), R255X (9.6%), and R294X (6.1%) in 115 patients with classical RTT. Two missense mutations, R133C (33.3%) and R306C (23.3%), and a nonsense mutation, R294X (13.3%), were common in 30 patients with atypical RTT, including the preserved speech variant (PSV). Frameshift mutations due to nucleotide deletion or insertion were identified in 22 patients with MECP2 mutations, and one of them had a 3.6 kb deletion encompassing exons 3 and 4. Three patients with classical RTT had a splicing anomaly. The wide spectrum of phenotypic variability in patients with RTT has been considered to be correlated with the mutation type and location in MECP2, and X-inactivation. However, most patients showed a random X-inactivation pattern evaluated by an androgen receptor gene polymorphism in this study, suggesting that a skewed X-inactivation might not be a main modification factor on clinical phenotypes of RTT. In addition, three new missense mutations, P176R, A378V and T479M, were identified in patients with RTT, but also in healthy Japanese, indicating that these mutations are non-pathogenic in Japanese. Information about rare polymorphic variations is very important for the molecular diagnosis of RTT, although rare polymorphic variants might differ among ethnic groups. (c) 2004 Elsevier B.V. All tights reserved.

    DOI: 10.1016/j.braindev.2004.06.003

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  • Relationship between severity of epilepsy and developmental outcome in Angelman syndrome 査読

    Y Ohtsuka, K Kobayashi, H Yoshinaga, T Ogino, I Ohmori, K Ogawa, E Oka

    BRAIN & DEVELOPMENT   27 ( 2 )   95 - 100   2005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 SCIENCE BV  

    To clarify the relationship between the degree of developmental disturbance and the severity of epilepsy in Angelman syndrome, we investigated 11 patients and measured both clinical outcomes and EEG parameters. Seven patients were followed up until after 8 years of age. Eight patients were found to have 15q11-q13 deletions.
    All patients experienced epileptic seizures and all but one displayed nonconvulsive status epilepticus (NCSE) during the period of observation. Epileptic seizures, including NCSE, disappeared by around 8 years of age. In addition, specific epileptic discharges, as measured by EEG, tended to subside with age. Although development seemed almost normal or only slightly delayed during the first 6 months of life, all patients eventually developed severe retardation. Two patients displayed very severe retardation and were unable to comprehend language or walk independently at the last follow-up. Only one patient was able to speak a few meaningful words. In one of the most severely affected patients, who showed the earliest onset of seizures and NCSE, it is possible that the repetitive bouts of NCSE might be responsible for the severe developmental outcome. However, the other patient with particularly severe retardation did not experience NCSE, while the patient with the most favorable outcome had repetitive episodes of NCSE.
    Therefore, we conclude that the severity of developmental disturbance in Angelman syndrome is not necessarily related to the degree of epilepsy. However, intensive therapy for NOSE might still be justified because there are some patients in whom NOSE results in a transient and sometimes permanent decline in mental and motor functioning.
    (C) 2004 Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.braindev.2003.09.015

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  • Relation between typical and borderline severe myoclonic epilepsy in infancy. 査読

    Y Ohtsuka, Ohmori, I, T Ogino, K Kobayashi, E Oka

    EPILEPSIA   46   11 - 12   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:BLACKWELL PUBLISHING INC  

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  • EEG in childhood absence epilepsy 査読

    H Yoshinaga, Y Ohtsuka, K Tamai, Tamura, I, M Ito, Ohmori, I, E Oka

    SEIZURE-EUROPEAN JOURNAL OF EPILEPSY   13 ( 5 )   296 - 302   2004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:W B SAUNDERS CO LTD  

    We performed a longitudinal clinico-electroencephalographic study of 23 children who were diagnosed as having absence epilepsy on their initial visits to our facility and we analysed those factors which lead to an unfavourable prognosis. Subjects and methods: We divided the 23 patients into three groups according to their clinical courses: Group A: eight patients who responded well to the therapy and became seizure free without relapse of epileptic discharges on EEGs; Group B: thirteen patients who suffered from relapse of epileptic discharges on EEGs despite clinical seizure cessation; Group C: two patients who continued to suffer from seizures. Results: (1) Fifty-six percent of all patients had focal epileptic discharges, including a surprising 63% of patients in Group A. (2) 'Lead in' in the ictal EEGs and automatisms during seizures were most commonly observed in patients in Group B, although there were no significant differences between the three groups. (3) The epilepsy of one patient in Group C evolved into complex partial seizures or absence status during her clinical course. She seemed to suffer from so-called 'frontal absence', despite the fact that her initial EEG did not show any focal abnormalities. (4) Patients in Group B were treated with tower AED dosages than those in Group A. In addition, one patient in Group C was treated irregularly. Conclusion: We conclude that it is not uncommon for patients with absence epilepsy to show focal abnormalities on EEGs and clinical ictal automatisms. Thus, the existence of clinical ictal automatisms and focal signs in electroencephalographic features are not sufficient indicators of the final outcome. Furthermore, it appears that regular and adequate drug therapy is important for a favourable prognosis. (C) 2003 BEA Trading Ltd. Published by Elsevier Ltd. All rights reserved.

    DOI: 10.1016/S1059-1311(03)00196-1

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  • Clinical and electroencephalographic characteristics of children with febrile seizures plus 査読

    K Kobayashi, Y Ohtsuka, I Ohmori, Y Nishio, M Fujiwara, M Ito, E Oka

    BRAIN & DEVELOPMENT   26 ( 4 )   262 - 268   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:ELSEVIER SCIENCE BV  

    Objectives: Febrile seizures plus (FS +) are attracting attention for their corresponding genetic abnormalities, and are defined as febrile seizures (FS) continuing beyond 6 years of age (late FS) or those associated with afebrile seizures. We tried to elucidate their clinical and EEG characteristics as compared with those of children having only FS. Subjects and methods: We reviewed clinical records in a pediatric neurology clinic to identify 31 patients with FS + (group FS +) and 51 with only FS (group FS). Their family history of seizures, clinical features and EEG findings were compared. Results: A family history of seizures was noted in 14 patients (45.2%) of group FS + and in 24 (47.1%) of group FS. In group FS +, 19 patients had late FS, 11 had afebrile seizures, and the remaining one had both types of seizures. Two patients had seizures induced by TV/video-game as well, and another suffered from absences. Epileptic EEG abnormalities, which included diffuse spike-waves and focal spikes, were noted in 13 patients (41.9%) of group FS + and 12 (23.5%) of group FS. Conclusions: The clinical and EEG characteristics of the children having FS + were diverse, without significant differences from those with FS except for the seizures types. (C) 2003 Elsevier B.V. All rights reserved.

    DOI: 10.1016/S0387-7604(03)00134-7

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  • Initiation of treatment and selection of antiepileptic drugs in childhood epilepsy 査読

    E Oka, T Murakami, T Ogino, T Kobayashi, Ohmori, I, T Akiyama, M Ito

    EPILEPSIA   45   17 - 19   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:WILEY-BLACKWELL  

    Purpose: A retrospective study was carried out on 53 cases with childhood epilepsy to evaluate the validity of the initial selection of antiepileptic drug (AED).
    Methods: We investigated the AEDs selected at the beginning of the treatment from the medical records of 53 untreated cases. A follow-up study was undertaken to evaluate the effects of the AEDs. In the second study, we investigated the AEDs of 10 cases with atypical benign partial epilepsy (ABPE), to clarify whether the initial AEDs selected for rolandic epilepsy were related to the appearance of ABPE.
    Results: The AEDs used at the initial stage consisted of carbamazepine (CBZ), valproic acid (VPA), phenobarbital (PB), and vitamin B-6. The main AEDs were CBZ and VPA for localization-related epilepsy, and VPA for generalized epilepsy. The initial selection of AEDs in 41 (85.4%) of 48 cases treated with AEDs were considered to be correct from the results of follow-up. We could not specify any AEDs that related to the appearance of ABPE.
    Conclusions: The selection of AED in this series was considered to be most appropriate. We proposed a criterion to determine whether to begin the AED treatment immediately at the initial seizure.

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  • Is phenotype difference in severe myoclonic epilepsy in infancy related to SCN1A mutations? 査読

    Ohmori, I, Y Ohtsukaa, M Ouchida, T Ogino, S Maniwa, K Shimizu, E Oka

    BRAIN & DEVELOPMENT   25 ( 7 )   488 - 493   2003年10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)   出版者・発行元:ELSEVIER SCIENCE BV  

    We classified 28 patients with severe myoclonic epilepsy in infancy (SME) according to the presence or absence of myoclonic seizures and/or atypical absences. Eleven of the patients had myoclonic seizures and/or atypical absences, and we refer to this condition as 'typical SME (TSME)'. Seventeen of the patients had only segmental myoclonias, and we refer to this condition as 'borderline SME (BSME)'. We then analyzed the electroclinical and genetic characteristics of these two groups. Ten of the 11 TSME patients had a photoparoxysmal response at some time during their clinical course, while none of the BSME patients showed this response. TSME and BSME showed a significant difference in regard to gender ratio: female dominance in TSME and male dominance in BSME (P = 0.008). The detection rate of the voltage-gated sodium channel alpha1-subunit (SCN1A) gene mutations was 72.7 and 88.2% in TSME and BSME, respectively. There was no difference in the type or rate of mutation between TSME and BSME. We conclude that TSME and BSME show distinct differences in photoparoxysmal response and gender, which might be caused by some genetic mechanism(s) other than the SCN1A gene mutation. (C) 2003 Elsevier Science B.V. All rights reserved.

    DOI: 10.1016/S0387-7604(03)00038-X

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  • Paroxysmal movement disorders in severe myoclonic epilepsy in infancy 査読

    Y Ohtsuka, Ohmori, I, T Ogino, M Ouchida, K Shimizu, E Oka

    BRAIN & DEVELOPMENT   25 ( 6 )   401 - 405   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 SCIENCE BV  

    We report on the electroclinical findings and the results of a molecular genetic study of a patient with typical severe myoclonic epilepsy ill infancy (TSME) and three with borderline SME (BSME) who showed paroxysmal movement disorders, such as choreoathetosis, dystonia and ballismus, during their clinical course. BSME was defined as a clinical entity that shares common characteristics with TSME but lacks myoclonic seizures associated with ictal EEG changes. When the paroxysmal movement disorders were first observed, all the patients in this study were being treated with polytherapy including phenytoin (PHT), and these abnormal movements disappeared when PHT was discontinued or reduced. However, on other occasions, two of our cases also showed the same abnormal movements even when not being treated with PHT. One patient with TSME and two of the three patients with BSME had SCN1A gene mutations that lead to truncation of the associated protein. We conclude that paroxysmal movement disorders seen in SME patients were closely related to their AED therapy, especially the use of PHT. It is thought that patients with both TSME and BSME have some predisposition toward paroxysmal movement disorders, and that this predisposition is partly related to sodium channel dysfunction, although some other factors might influence the occurrence of this phenomenon. (C) 2003 Elsevier Science B.V. All rights reserved.

    DOI: 10.1016/S0387-7604(03)00025-1

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  • Significant correlation of the SCN1A mutations and severe myoclonic epilepsy in infancy 査読

    Ohmori, I, M Ouchida, Y Ohtsuka, E Oka, K Shimizu

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   295 ( 1 )   17 - 23   2002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:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    To investigate the possible correlation between genotype and phenotype of epilepsy, we analyzed the voltage-gated sodium channel alpha1-subunit (SCNIA) gene, beta1-subunit (SCN1B) gene, and gamma-aminobutyric acidA receptor gamma2-subunit (GABRG2) gene in DNAs from peripheral blood cells of 29 patients with severe myoclonic epilepsy in infancy (SME) and 11 patients with other types of epilepsy. Mutations of the SCNIA gene were detected in 24 of the 29 patients (82.7%) with SME, although none with other types of epilepsy. The mutations included deletion, insertion, missense, and nonsense mutations. We could not find any mutations of the SCN1B and GABRG2 genes in all patients. Our data suggested that the SCNIA mutations were significantly correlated with SME (p &lt; .0001). As we could not find SCNIA mutations in their parents, one of critical causes of SME may be de novo mutation of the SCNIA gene occurred in the course of meiosis in the parents. (C) 2002 Elsevier Science (USA). All rights reserved.

    DOI: 10.1016/S0006-291X(02)00617-4

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  • The relationship between paroxysmal kinesigenic choreoathetosis and epilepsy 査読

    Ohmori, I, Y Ohtsuka, T Ogino, H Yoshinaga, K Kobayashi, E Oka

    NEUROPEDIATRICS   33 ( 1 )   15 - 20   2002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:GEORG THIEME VERLAG KG  

    Purpose: To clarify the relationship between paroxysmal kinesigenic choreoathetosis (PKC) and epilepsy, we investigated the clinical and electroencephalographic (EEG) findings of patients with familial PKC and epilepsy, as well as sporadic cases with both PKC and epilepsy.
    Patients and Methods: Patients consisted of 12 familial cases from seven families and three sporadic cases. The period of follow-up ranged from 17 months to 33 years, 7 months (average: 16 years, 8 months). During the follow-up, a total of 163 EEGs (11 EEGs per subject) were studied, including interictal and ictal EEGs.
    Results: Transient epileptic discharges were found in ten of the 15 patients (66.7%) during the clinical course. As for focus, centro-midtemporal and frontal spikes were most often observed. The ictal EEG of an afebrile convulsion in one patient showed a partial seizure with secondary generalization which originated from the frontal area.
    Conclusions: It appears that patients who suffer from both PKC and epilepsy have a functional abnormality of the cerebral cortex, particularly in the perirolandic and frontal regions.

    DOI: 10.1055/s-2002-23594

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  • A population-based neuroepidemiological survey of West syndrome in Okayama Prefecture, Japan 査読

    E Oka, N Murakami, Ohmori, I, T Ogino

    BRAIN & DEVELOPMENT   23 ( 7 )   580 - 583   2001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 SCIENCE BV  

    It is important for the fields of child neurology and child public health to clarify the prevalence and incidence rates of West syndrome because this syndrome is a major cause of developmental disorders.
    However, there have been few reports in Japan on the prevalence rate of West syndrome in the general population.
    We carried out a population-based survey in Okayama Prefecture, in western Japan in 1994. The Population under 2 years of age in Okayama Prefecture in 1994 was 37,085. Six cases of West syndrome were identified. The prevalence rate was 0.16 per 1000. (C) 2001 Elsevier Science BN. All rights reserved.

    DOI: 10.1016/S0387-7604(01)00273-X

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  • Clinical spectrum of epileptic spasms associated with cortical malformation 査読

    K Kobayashi, Y Ohtsuka, S Ohno, Ohmori, I, T Ogino, H Yoshinaga, A Tanaka, Y Hiraki, E Oka

    NEUROPEDIATRICS   32 ( 5 )   236 - 244   2001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:GEORG THIEME VERLAG KG  

    sThe spectrum of clinico-electrical characteristics of epileptic spasms associated with cortical malformation was studied in detail. The subjects were 15 patients suffering from spasms and cortical malformation demonstrated by MRI. The types of cortical malformation causing spasms were various, including hemimegalencephaly, diffuse pachygyria, focal cortical dysplasia, and polymicrogyria. Ohtahara syndrome was diagnosed in 3 patients, and West syndrome in 8. Symptomatic localization-related epilepsy preceded West syndrome in 4 patients, and a transition from Ohtahara syndrome to West syndrome was observed in one. West syndrome was followed by symptomatic generalized epilepsy including Lennox-Gastaut syndrome in 4 patients. Nine patients showed a condition which was labeled "epilepsy with partial seizures and spasms" (EPS) and characterized by the coexistence of partial seizures and spasms, and multifocal epileptic discharges on EEG. Spasms occurred only as EPS in 5 patients. EPS appeared following Ohtahara syndrome or West syndrome in 4 patients, and showed a transition to symptomatic localization-related epilepsy in 4. However, EPS did not evolve into generalized epilepsy, and persisted until the time of last follow-up in 5 patients. Therefore, the clinico-electrical pictures of patients with spasms and cortical malformation were diverse and not always limited within those of typical generalized epilepsy.

    DOI: 10.1055/s-2001-19117

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  • Analysis of ictal EEGs of epilepsy associated with tuberous sclerosis 査読

    Ohmori, I, Y Ohtsuka, S Ohno, E Oka

    EPILEPSIA   39 ( 12 )   1277 - 1283   1998年12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)   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

    Purpose: To investigate the significance of cortical pathology of tonic spasms in patients with tuberous sclerosis.
    Methods: The subjects were 38 patients with epilepsy associated with tuberous sclerosis. We analyzed ictal EEGs of tonic spasms and partial seizures by means of video-EEG monitoring for a total of 763 tonic spasms in 20 patients and 107 partial seizures in 15 patients. We also investigated the relation between partial seizures and magnetic resonance imaging (MRI) findings of these patients.
    Results: Ictal EEG patterns of tonic spasms were divided into generalized and focal patterns. Thirteen patients had only generalized patterns, whereas seven had both patterns. In five patients who had focal ictal patterns of tonic spasms and partial seizures, the location of focal patterns corresponded with the location of onset of partial seizures. Focal discharges were seen immediately before, after, and in the middle of tonic spasms in series in 13 patients. The location of focal discharges also corresponded with the location of the onset of partial seizures in 10 of the 13 patients. Regarding partial seizures, four patients had multiple active epileptogenic foci during the same period, and two others had shifting epileptogenic foci with increasing age.
    Conclusions: These findings indicate that cortical pathology plays an important role in the occurrence not only of partial seizures but also of tonic spasms in patients with tuberous sclerosis.

    DOI: 10.1111/j.1528-1157.1998.tb01325.x

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  • Long-term follow-up of childhood epilepsy associated with tuberous sclerosis 査読

    Y Ohtsuka, Ohmori, I, E Oka

    EPILEPSIA   39 ( 11 )   1158 - 1163   1998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:LIPPINCOTT WILLIAMS & WILKINS  

    Purpose: To study the clinical and electroencephalographic (EEG) characteristics of patients whose epilepsy is associated with tuberous sclerosis, with special reference to their clinical course.
    Methods: We investigated the electroclinical and radiologic features of 38 patients with epilepsy associated with tuberous sclerosis.
    Results: Eleven patients showed only generalized epilepsy, and 10 showed only localization-related epilepsy throughout their clinical course. Among the other 17 cases, the nature of the epilepsy changed between generalized and localization-related epilepsies during the clinical course. A shift from generalized to localization-related epilepsies was more common than the reverse. Seventeen had West syndrome (WS), three had Lennox-Gastaut syndrome (LGS), and eight had epilepsies that evolved from WS to LGS. Tonic spasms, mostly in series, were seen in all 28 patients with generalized epilepsy. Eleven of the 28 patients had partial seizures and tonic spasms in the same period. Six of them showed "simultaneous seizures," consisting of tonic spasms in series and a partial seizure. Partial seizures were the main seizure type in 27 patients with localization-related epilepsy, but three of them also showed tonic spasms that included "simultaneous seizures." Ictal EEGs revealed multiple active foci in the same period that could shift during the clinical course. Neither the location nor number of tubers was related to the clinical course. As for seizure outcome, 12 (32%) of 38 patients were free from seizures at follow-up.
    Conclusions: In epilepsies associated with tuberous sclerosis, there may be an interrelation between generalized and localization-related epilepsies, as well as one between generalized and partial seizures.

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  • Electroclinical study of localization-related epilepsies in early infancy 査読

    Ohmori, I, Y Ohtsuka, E Oka, T Akiyama, S Ohtahara

    PEDIATRIC NEUROLOGY   16 ( 2 )   131 - 136   1997年2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)   出版者・発行元:ELSEVIER SCIENCE INC  

    To clarify the characteristics of localization-related epilepsies in early infancy, we performed an electroclinical study of 28 epileptic patients whose first seizures occurred before 6 months of age. The patients were retrospectively divided into two groups: the seizure-controlled group (8 patients) and the refractory group (20 patients). The seizure-controlled group included the patients whose seizures were suppressed within 1 year after onset; the refractory group included all other patients. The characteristics of the refractory group were as follows: (1) most patients had serious underlying pathologies; (2) the seizure type in most cases was simple partial seizure or complex partial seizure without secondary generalization; (3) the interictal EEG showed focal abnormalities and severe dysrhythmia on the basic pattern associated with multifocal spikes in most cases; and (4) in some patients, West syndrome developed after localization- related epilepsies and generalized seizures appeared later in some cases. (C) 1997 by Elsevier Science Inc.

    DOI: 10.1016/S0887-8994(96)00296-2

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  • Estimation of obscure ictal epileptic activity in scalp EEG 査読

    Katsuhiro Kobayashi, Tomoyuki Nakahori, Iori Ohmori, Harumi Yoshinaga, Yoko Otsuka, Eiji Oka, Shunsuke Ohtahara

    Brain Topography   9 ( 2 )   125 - 134   1996年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    We have produced a method to estimate ictal localized epileptic activity hidden among the background in scalp EEGs. When the visually completely different waveforms of the epileptic and background activities are nearly orthogonal, epileptic activity may be approximately extracted from the EEG data matrix by singular value decomposition with subsequent orthogonal rotation to match the distribution of one component with that of the epileptic source. A simulation study was carried out using a matrix mimicking the scalp EEG with an inconspicuous ictal epileptic activity from a dipole source. This hidden epileptic activity was approximately recovered by matching the dipole of interest with the epileptic dipole, even when the simulated waveforms of the epileptic and background activities were not exactly orthogonal. High linear correlation between these two types of waveforms hampered the recovery of the epileptic activity. In another simulation study employing two epileptic dipoles producing activities with the same waveform and a brief time lag, it was indicated that the temporal relationship between the epileptic activities could be also estimated using the cross-correlation function. In the preliminary clinical application of this method to the ictal EEGs of complex partial seizures, rhythmic activities with seemingly epileptic waveforms were estimated at the dipoles which were located in the vicinity of cortical lesions revealed by neuroimaging studies. These activities were indicated to appear before any change in the scalp EEG. We hope for the clinical application of this method for noninvasive estimation of inconspicuous ictal epileptic activity.

    DOI: 10.1007/BF01200712

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  • THE GENERATIVE PROCESS OF EPILEPTIC HIGH-FREQUENCY OSCILLATIONS AS SHOWN THROUGH NEURONAL NETWORK SIMULATION OF THE RAT DENTATE GYRUS

    K. Kobayashi, T. Akiyama, Ohmori, I, T. Inoue, H. Yoshinaga

    EPILEPSIA   54   46 - 46   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)   出版者・発行元:WILEY-BLACKWELL  

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  • CACNA1A VARIANTS AS A POTENTIAL GENETIC MODIFIER OF DRAVET SYNDROME

    Ohmori, I, M. Ouchida, K. Kobayashi, Y. Ohtsuka, H. Matsui

    EPILEPSIA   54   195 - 196   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)   出版者・発行元:WILEY-BLACKWELL  

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  • Development of Tumor Specific Killing eGFP Peptide gainst Malignant Brain Tumor

    Miroyuki Michiue, Shiori Akada, Hideki Matsui, Tei-ichi Nishiki, Iori Ohmori, Akimasa Yamaguchi, Mizuki Kitamatsu

    BIOPOLYMERS   100 ( 3 )   255 - 255   2013年5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  

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  • オキシトシンの抗うつ作用に関わるマウス海馬神経細胞内シグナル伝達経路

    松崎 光博, 松下 博昭, 韓 小建, 沖本 直輝, 道上 宏之, 西木 禎一, 大守 伊織, 富澤 一仁, 松井 秀樹

    日本生理学雑誌   74 ( 2 )   46 - 46   2012年3月

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    記述言語:日本語   出版者・発行元:(一社)日本生理学会  

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  • 急性脳症における遺伝性けいれん素因とSCN1A遺伝子変異

    大守 伊織, 小林 勝弘, 大内田 守, 奥村 彰久, 前垣 義弘, 西山 逸子, 大塚 頌子

    脳と発達   43 ( Suppl. )   S352 - S352   2011年5月

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    記述言語:英語   出版者・発行元:(一社)日本小児神経学会  

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  • The neuroprotective effects of GDNF-pretreatment for neural stem cell transplantation in the 6-OHDA-lesioned rats

    Feifei Wang, Hiroyuki Michiue, Masahiro Kameda, Teiichi Nishiki, Iori Ohmori, Isao Date, Hideki Matsui

    NEUROSCIENCE RESEARCH   71   E137 - E138   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.2011.07.592

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  • Ca2+-dependent dissociation of synaptotagmin I from SNARE complexes

    Koichiro Suzuki, Toshio Masumoto, Iori Ohmori, Hiroyuki Michiue, Tei-ichi Nishiki, Hideki Matsui

    NEUROSCIENCE RESEARCH   71   E314 - E314   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.2011.07.1372

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  • Electrophysiological properties of variant voltage-gated calcium channels in patients with epilepsy

    Iori Ohmori, Mamoru Ouchida, Haijiao Wang, Yuichiro Kitagawa, Hiroyuki Michiue, Teiichi Nishiki, Hideki Matsui

    NEUROSCIENCE RESEARCH   71   E294 - E294   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.2011.07.1284

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  • Sildenafil exerts oxytocin-receptor-mediated antidepressant effects in male mice via a pathway involving MAP kinase and CREB phosphorylation in hippocampus

    Mitsuhiro Matsuzaki, Hiroaki Matsushita, Xiao-Jian Han, Tei-ichi Nishiki, Iori Ohmori, Kazuhito Tomizawa, Hideki Matsui

    NEUROSCIENCE RESEARCH   71   E302 - E302   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.2011.07.1317

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  • Metabolic and respiratory acidosis suppresses absence seizures in Cacna1a mutant rats

    Mamoru Ouchida, Yuko Kaida, Iori Ohmori, Takashi Uehara, Hideki Matsui

    NEUROSCIENCE RESEARCH   71   E296 - E296   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.2011.07.1293

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  • オキシトシンはマウスでの交尾行動ならびにシルデナフィルによる抗うつ効果に関与する(Oxytocin mediates antidepressant effect by mating behavior and sildenafil in mice)

    松下 博昭, 松崎 光博, 富澤 一仁, 沖本 直輝, 西木 禎一, 大守 伊織, 松井 秀樹

    神経化学   49 ( 2-3 )   675 - 675   2010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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  • 神経伝達物質放出に関わるシナプトタグミン1とSNARE複合体の結合部位の同定

    西木 禎一, 増本 年男, 大守 伊織, 富澤 一仁, 松井 秀樹

    日本生理学雑誌   72 ( 4 )   131 - 132   2010年4月

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    記述言語:日本語   出版者・発行元:(一社)日本生理学会  

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  • オキシトシンは雄マウスでの交尾行動ならびにシルデナフィルによる抗うつ効果に関与する

    松下 博昭, 富澤 一仁, 沖本 直輝, 西木 禎一, 大守 伊織, Bosch O, Neumann ID, 松井 秀樹

    日本生理学雑誌   72 ( 4 )   132 - 132   2010年4月

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    記述言語:日本語   出版者・発行元:(一社)日本生理学会  

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  • A CACNB4 mutation shows altered Cav2.1 function in a patient with Dravet syndrome

    大守伊織, 大内田守, 御牧信義, 西木禎一, 富澤一仁, 松井秀樹

    岡山医学会雑誌   121 ( 3 )   149 - 156   2010年

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  • ナトリウムチャネル遺伝子Scn1a変異ラットの開発解析研究

    芹川忠夫, 大守伊織, 大内田守, 大野行弘, 鶴見東志子, 三木崇史, 若森実, 石原靜, 吉田卓史, 滝沢明子, 加藤めぐみ, 平林真澄, 笹征史, 森泰生, 真下知士

    てんかん治療研究振興財団研究年報   21   29 - 36   2010年

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  • Oxytocin mediates antidepressant effect by mating behavior and sildenafil in mice

    Hiroaki Matsushita, Mitsuhiro Matsuzaki, Kazuhito Tomizawa, Naoki Okimoto, Tei-ich Nishiki, Iori Ohmori, Hideki Matsui

    NEUROSCIENCE RESEARCH   68   E315 - E315   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.2010.07.1398

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  • Ca2+-dependent dissociation of syntaxin 1 from synaptotagmin 1

    Toshio Masumoto, Telichi Nishiki, Iori Ohmori, Kazuhito Tomizawa, Hideki Matsui

    JOURNAL OF PHYSIOLOGICAL SCIENCES   60   S127 - S127   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:SPRINGER TOKYO  

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  • Assembly and disassembly of the complex of synaptotagmin 1 and syntaxin 1 under physiological conditions

    Toshio Masumoto, Tei-ichi Nishiki, Iori Ohmori, Hideki Matsui

    NEUROSCIENCE RESEARCH   68   E228 - E228   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.2010.07.1007

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  • Effects of antiepileptic drugs on febrile seizures in Scnl a mutant rats

    Keiichiro Hayashi, Iori Ohmori, Teiichi Nishiki, Tomoji Mashimo, Tadao Serikawa, Hideki Matsui

    JOURNAL OF PHYSIOLOGICAL SCIENCES   60   S203 - S203   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:SPRINGER TOKYO  

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  • Dravet症候群患者に認められたカルシウムチャネル機能異常を引き起こすCACNB4遺伝子変異

    大守 伊織, 大内田 守, 御牧 信義, 西木 禎一, 富澤 一仁, 松井 秀樹

    岡山医学会雑誌   121 ( 3 )   149 - 156   2009年12月

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    記述言語:日本語   出版者・発行元:岡山医学会  

    Dravet症候群患者に認められたカルシウムチャネル機能異常を引き起こすCACNB4遺伝子変異について検討した。SCN1A遺伝子解析で変異を認めたDravet症候群患者38例を対象とした。健常者200例を対照とした。Dravet症候群患者で、SCN1B遺伝子とGABRG2遺伝子に変異を持つ症例はなかったが、CACNB4遺伝子変異を持つ症例を1例見出した。全細胞記録では、R568X変異からは背景電流異常のナトリウム電流は認めなかった。変異チャネルが野生型に比し有意にBa2+電流が増大した。ピーク電圧、細胞キャパシタンス、電流密度も変異型が野生型よりも有意に高値であった。

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  • オキシトシンによる不安情動作用機構の解明

    沖本 直輝, 大森 正泰, 西木 禎一, 大守 伊織, 平松 祐司, 松井 秀樹, 富澤 一仁

    日本生理学雑誌   71 ( 3 )   153 - 153   2009年3月

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    記述言語:日本語   出版者・発行元:(一社)日本生理学会  

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  • A CONSTITUTIVELY ACTIVE CALCINEURIN ENCODED BY AN INTRON-RETAINING MESSENGER RNA IS REQUIRED FOR HAIR FOLLICLE DEVELOPMENT

    Atsushi Fujimura, Kazuhito Tomizawa, Hiroyuki Michiue, Tei-ichi Nishiki, Iori Ohmori, Hideki Matsui

    JOURNAL OF PHYSIOLOGICAL SCIENCES   59   244 - 244   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:SPRINGER TOKYO  

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  • MOLECULAR MECHANISM OF THE REGULATION OF ANTI-ANXIETY BY OXYTOCIN

    Naoki Okimoto, Kazuhito Tomizawa, Teiichi Nishiki, Iori Ohmori, Hideki Matsui

    JOURNAL OF PHYSIOLOGICAL SCIENCES   59   280 - 280   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:SPRINGER TOKYO  

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  • DELIVERY OF SODIUM BOROCAPTATE TO GLIOMA CELLS USING IMMUNOLIPOSOME CONJUGATED WITH ANTI-EGFR ANTIBODIES BY ZZ-HIS

    Bin Feng, Kazuhito Tomizawa, Hiroyuki Michiue, Xiao-Jian Han, Atsushi Fujimura, Iori Ohmori, Tei-ichi Nishiki, Hideki Matsui

    JOURNAL OF PHYSIOLOGICAL SCIENCES   59   441 - 441   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:SPRINGER TOKYO  

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  • MICE OVEREXPRESSING DOMINANT NEGATIVE Cdk5 IN THE PANCREATIC BETA CELLS SHOW THE DIABETES MELLITUS

    Yoshihiro Ohtani, Kazuhito Tomizawa, Toshio Ohshima, Hiroyuki Michiue, Teiichi Nishiki, Iori Ohmori, Hideki Matsui

    JOURNAL OF PHYSIOLOGICAL SCIENCES   59   532 - 532   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:SPRINGER TOKYO  

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  • Oxytocin mediates mating-induced antidepressant effect in male mice

    Hiroaki Matsushita, Kazuhito Tomizawa, Naoki Okimoto, Iori Ohmori, Tei-ichi Nishiki, Hideki Matsui

    NEUROSCIENCE RESEARCH   65   S254 - S254   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.2009.09.1444

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  • J-1 A screening test for the prediction of Dravet syndrome before one year of age(The 42^<nd> Congress of the Japan Epilepsy Society)

    服部旬里, 大内田守, 大野順子, 三宅進, 真庭聡, 御牧信義, 大塚頒子, 大守伊織

    てんかん研究   26 ( 2 )   2008年9月

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    出版者・発行元:日本てんかん学会  

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  • 膵β細胞特異的ドミナントネガティブCdk5発現トランスジェニックマウスの作製

    大谷 理浩, 富澤 一仁, 大島 登志男, 西木 禎一, 大守 伊織, 御子柴 克彦, 松井 秀樹

    日本生理学雑誌   70 ( 2 )   73 - 74   2008年2月

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    記述言語:日本語   出版者・発行元:(一社)日本生理学会  

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  • カルシニューリンAβの恒常的活性体は発毛メカニズムに関与する

    藤村 篤史, 富澤 一仁, 西本 禎一, 大守 伊織, 松井 秀樹

    日本生理学雑誌   70 ( 2 )   74 - 74   2008年2月

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    記述言語:日本語   出版者・発行元:(一社)日本生理学会  

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  • Pharmacological effects of antiepileptic drugs on mutant Nav1.1 channels associated with epilepsy

    Iori Ohmori, Hiroaki Matsushita, Teiichi Nishiki, Kazuhito Tomizawa, Hideki Matsui

    NEUROSCIENCE RESEARCH   61   S128 - S128   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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  • J-2 Nonfunctional SCN 1 A Is Common in Severe Myoclonic Epilepsy of Infancy(The 41^<th> Congress of the Japan Epilepsy Society)

    大守伊織, KMKahlig, THRhodes, DWWang, ALJr.George

    てんかん研究   25 ( 3 )   2007年9月

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    出版者・発行元:日本てんかん学会  

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  • CaMKIを介したDrop1リン酸化によるミトコンドリア形態制御

    韓 小建, 松下 正之, 富澤 一仁, 西木 禎一, 大守 伊織, 松井 秀樹

    日本生理学雑誌   69 ( 3 )   126 - 126   2007年3月

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    記述言語:英語   出版者・発行元:(一社)日本生理学会  

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  • 脳腫瘍を標的としたバイオナノカプセルの開発

    筒井 佑美, 富澤 一仁, 西木 禎一, 大守 伊織, 名木田 真奈, 妹尾 昌治, 松井 秀樹

    日本生理学雑誌   69 ( 3 )   125 - 125   2007年3月

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    記述言語:日本語   出版者・発行元:(一社)日本生理学会  

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  • SCN1A missense mutation associated with infantile partial epilepsy

    Iori Ohmori, Mamoru Ouchida, Katsuhiro Kobayashi, Yoko Ohtsuka, Kenji Shimizu, Teiichi Nishiki, Kazuhito Tomizawa, Hideki Matsui

    NEUROSCIENCE RESEARCH   58   S187 - S187   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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  • オキシトシンによるProtein kinase C発現制御

    藤田 梨嘉, 魏 范研, 富澤 一仁, 松下 正之, 大守 伊織, 松井 秀樹

    日本生理学雑誌   68 ( 5 )   183 - 183   2006年5月

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    記述言語:日本語   出版者・発行元:(一社)日本生理学会  

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  • Cdk5によるインスリン分泌制御機構

    魏 范研, 富澤 一仁, 佐伯 恭範, 松下 正之, 大守 伊織, 松井 秀樹

    日本生理学雑誌   68 ( 5 )   185 - 185   2006年5月

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    記述言語:日本語   出版者・発行元:(一社)日本生理学会  

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  • Pharmacological rescue of trafficking defective Nav1.1 channels

    Iori Ohmori, Teiichi Nishiki, Kazuhito Tomizawa, Hideki Matsui

    NEUROSCIENCE RESEARCH   55   S141 - S141   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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  • Calpain inhibits endocytosis by cleaving amphiphysin I

    Yumei Wu, Kazuhito Tomizawa, Shuang Liang, Iori Ohmori, Teiichi Nishiki, Kohji Takei, Hideki Matsui

    NEUROSCIENCE RESEARCH   55   S76 - S76   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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  • Relationship between absence seizures and GABA(A) receptor.

    M Ito, I Ohmori, T Nakahori, T Takata, H Yoshinaga, Y Ohtsuka

    EPILEPSIA   46   16 - 16   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:BLACKWELL PUBLISHING  

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  • てんかん外科手術後に間けつ性爆発性障害を呈した内側側頭葉てんかんの2例

    和田健, 山田了士, 鈴木啓嗣, 黒田重利, 榎日出夫, 大守伊織, 真柳佳昭

    精神医学   46 ( 9 )   947 - 953   2004年9月

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    記述言語:日本語  

    DOI: 10.11477/mf.1405100547

    J-GLOBAL

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  • MECP2 mutations in 217 patients with RTT syndrome.

    Kondo, I, Ishihara, I, M Miyamoto, T Matsuishi, Y Yamashita, K Kuwajima, T Iwai, S Endo, M Sone, H Yamagata, Y Tabara, Ohmori, I, E Oka

    AMERICAN JOURNAL OF HUMAN GENETICS   73 ( 5 )   333 - 333   2003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)   出版者・発行元:UNIV CHICAGO PRESS  

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  • P-01 乳児重症ミオクロニーてんかんの中核群と辺縁群の関連

    大塚頌子, 大守伊織, 荻野竜也, 小林勝弘, 岡〓次

    日本てんかん学会プログラム・予稿集   ( 37 )   2003年10月

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    出版者・発行元:日本てんかん学会  

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  • 徐波睡眠時に持続性棘徐波を示すてんかんおよびその近縁状態の治療

    犬塚幹, 大塚頌子, 小林勝弘, 大守伊織, 岡〓次

    日本てんかん学会プログラム・予稿集   ( 36 )   2002年9月

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    出版者・発行元:日本てんかん学会  

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  • Mutation spectrum and genotype-phenotype correlation of MECP2 in 100 Japanese patients with Rett syndrome.

    T Fukuda, T Matsuichi, R Morishita, Y Yamashita, Ohmori, I, Horiuchi, I, K Kuwajima, H Nitta, H Yamagata, Kondo, I

    AMERICAN JOURNAL OF HUMAN GENETICS   69 ( 4 )   595 - 595   2001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:UNIV CHICAGO PRESS  

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  • A-10 多小脳回に合併するてんかんの特徴

    大塚頌子, 小林勝弘, 太田穂高, 大守伊織, 榎日出夫, 吉永治美, 岡〓次

    日本てんかん学会プログラム・予稿集   ( 34 )   2000年9月

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    出版者・発行元:日本てんかん学会  

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  • B-13 複雑部分発作の発作時脳波の有用性と限界

    吉永治美, 大守伊織, 浅野孝, 秋山倫之, 岡〓次

    日本てんかん学会プログラム・予稿集   ( 34 )   2000年9月

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    出版者・発行元:日本てんかん学会  

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  • てんかん外科手術後に著明な衝動性こう進を呈した側頭葉てんかんの2例

    和田健, 山田了士, 河本俊彦, 鈴木啓嗣, 黒田重利, 榎日出夫, 大守伊織

    てんかん研究   18 ( 1 )   49   2000年2月

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    記述言語:日本語  

    J-GLOBAL

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  • 閉眼過敏および図形過敏反応出現時の鳥距溝動脈血流速度

    眞田 敏, 大守伊織, 太田穂高, 寺崎智行

    臨床脳波   42 ( 1 )   61 - 64   2000年

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  • 難治てんかんに対するmexiletineの適応に関する検討

    榎日出夫, 畑寛信, 大守伊織, 眞庭聡, 太田穂高, 小林勝弘

    脳と発達   32 ( 1 )   29 - 34   2000年

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  • B-22 てんかん外科手術後に著名な衝動性亢進を呈した側頭葉てんかんの2例

    和田健, 山田了士, 河本俊彦, 鈴木啓嗣, 黒田重利, 榎日出夫, 大守伊織

    日本てんかん学会プログラム・予稿集   ( 33 )   1999年10月

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    出版者・発行元:日本てんかん学会  

    CiNii Article

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  • E-24 乳児重症ミオクロニーてんかんの発作時脳波分析

    大守伊織, 大塚頌子, 村上暢子, 浅野孝, 服部旬里, 岡〓次

    日本てんかん学会プログラム・予稿集   ( 33 )   1999年10月

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    出版者・発行元:日本てんかん学会  

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  • Epilepsy with subcontinuous spike-waves during sleep and focal cortical dysplasia.

    Y Ohtsuka, T Asano, Ohmori, I, K Kobayashi, H Yoshinaga, E Oka

    EPILEPSIA   40   233 - 234   1999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:LIPPINCOTT WILLIAMS & WILKINS  

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  • Relationship between cortical tubers and clinical features in patients with tuberous sclerosis.

    Ohmori, I, Y Ohtsuka, T Asano, E Oka, A Tanaka, S Hiraki

    EPILEPSIA   40   229 - 229   1999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:LIPPINCOTT WILLIAMS & WILKINS  

    Web of Science

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  • B-20 難治てんかんに対するロフラゼプ酸エチルの効果

    村上暢子, 吉永治美, 大守伊織, 小川和則, 浅野孝, 岡

    日本てんかん学会プログラム・予稿集   ( 32 )   1998年10月

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    出版者・発行元:日本てんかん学会  

    CiNii Article

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  • Angelman症候群における誘発電位について

    眞田敏, 小川和則, 大守伊織, 荻野竜也, 石田喬士

    研究集録   108   37 - 40   1998年7月

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    出版者・発行元:岡山大学  

    CiNii Article

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  • 生後6カ月未満発症の局在関連性てんかんに関する研究

    大守伊織

    岡山醫學會雜誌   107 ( 7 )   99 - 109   1995年8月

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    出版者・発行元:岡山医学会,Okayama Medical Association  

    To clarify the characteristics of localization-related epilepsies occurring before 6 monthes of age, I carried out an electroclinical study on 28 cases which had been followed up for more than one year after the onset. The subjects were divided into two groups : the controlled group (8 cases) and the refractory group (20 cases). The controlled group was defined as the subjects whose seizures were suppressed within one year after the onset and the other subjects were classified into the refractory group. The characteristies of the refractory group were as follows : Most cases had serious und...

    DOI: 10.4044/joma1947.107.7-8_99

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  • SEIZURES IN SERIES OBSERVED IN SYMPTOMATIC GENERALIZED EPILEPSY OTHER THAN WEST SYNDROME

    M MIZUKAWA, OHMORI, I, Y OHTSUKA, E OKA, S OHTAHARA

    EPILEPSIA   36   S202 - S202   1995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:LIPPINCOTT-RAVEN PUBL  

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  • 2C-12 生後6ヶ月未満発症の小児てんかんの特異性

    大守伊織, 村嶋逸子, 吉永治美, 大塚頌子, 大田原俊輔

    日本てんかん学会プログラム・予稿集   ( 27 )   1993年10月

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    出版者・発行元:日本てんかん学会  

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講演・口頭発表等

  • チオレドキシンの機能低下は神経細胞とオリゴデンドロサイトの細胞死を惹起する

    大守伊織, 大内田守, 今井宏彦, 豊國伸哉,真下知士

    第44回 日本分子生物学会  2021年12月3日 

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    記述言語:英語   会議種別:ポスター発表  

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  • 慢性腎臓病を伴う早発老化モデル動物の発見

    大内田守, 大守伊織, 豊國伸哉, 真下知士

    第44回 日本分子生物学会  2021年12月 

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  • Cacna1a遺伝子変異はScn1a遺伝子変異ラットの表現型を変化させる

    大守伊織, 大内田守, 小林聖佳

    日本人類遺伝学会第65回大会  2020年11月 

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  • てんかんモデルラットにおける親子間の行動異常

    大守伊織

    第62回 日本小児神経学会学術集会  2020年8月 

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  • Txn1遺伝子ミスセンス変異をもつ新規CKDモデルラット

    大守伊織, 真下知士, 大内田守, 豊國伸哉

    日本腎臓病学会  2019年6月21日 

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    記述言語:日本語   会議種別:ポスター発表  

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  • A novel model rat of chronic kidney disease

    Ohmori I, Mashimo T, Ouchida M, Toyokuni S

    Federation of the Asian and Oceanian Physiological Societies  2019年3月28日 

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    記述言語:英語   会議種別:ポスター発表  

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  • 新規Txn1遺伝子ミスセンス変異による多臓器障害

    大守伊織, 真下知士, 大内田守, 山下享子, 豊國伸哉

    2018年5月17日 

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    記述言語:日本語   会議種別:ポスター発表  

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  • GEFS+モデルラットの分子病態基盤と臨床応用 招待

    大守伊織

    第51回日本てんかん学会学術集会  2017年11月5日 

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    記述言語:日本語   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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  • Approach from basic and molecular study “Electrophysiological study of hyperthermia-induced seizures in Scn1a mutant rats 招待

    大守伊織

    第94回日本生理学会大会  2017年3月29日 

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    記述言語:英語   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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産業財産権

  • 遺伝子改変非ヒトモデル動物

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    出願人:大守伊織,大内田守,真下知士

    出願番号:特願2019-514326 

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  • 抗てんかん薬

    大守伊織

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    出願番号:特願2015-522706  出願日:2014年5月28日

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  • てんかん波を伴う疾患治療剤

    大守伊織

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    出願番号:特願2012-525374  出願日:2011年7月12日

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  • Dravet 症候群の発症可能性の判定方法およびその利用

    大守伊織

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    出願番号:特願2011-551907  出願日:2011年1月27日

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  • Dravet 症候群の早期診断を可能にするためのデータを取得する方法及びその利用

    大守伊織, 大内田守, 大塚頌子

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    出願番号:特願2007-007449  出願日:2007年1月16日

    公開番号:特開2008-173193 

    特許番号/登録番号:特許4461263  発行日:2010年2月26日

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受賞

  • 優秀演題賞

    2018年5月   日本酸化ストレス学会  

    大守伊織

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  • Gold Poster賞

    2013年6月   国際てんかん学会  

    大守伊織

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  • 新見賞

    2009年6月   岡山医学会  

    大守伊織

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  • Juhn and Mary Wada奨励賞

    2007年11月   日本てんかん学会  

    大守伊織

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  • てんかん治療研究振興財団研究褒賞

    2007年3月  

    大守伊織、大内田守

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  • 学術奨励賞

    2000年2月   岡山県医学会  

    大守伊織

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共同研究・競争的資金等の研究

  • 抗腫瘍剤の開発

    2020年04月 - 2022年03月

    橋渡し研究推進戦略的プログラム 

    大内田守, 大守伊織

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    担当区分:研究分担者 

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  • 新規モデルラットを用いたウエスト症候群の発症機序の解明

    研究課題/領域番号:16H05354  2016年04月 - 2020年03月

    日本学術振興会  科学研究費助成事業 基盤研究(B)  基盤研究(B)

    大内田 守, 大守 伊織

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    配分額:17030000円 ( 直接経費:13100000円 、 間接経費:3930000円 )

    申請者らは点突然変異誘発剤処理したラットから生まれた系統群の表現型解析研究を続けた結果、発達性およびてんかん性脳症に酷似した症状を示す疾患ラットを見出した。当疾患ラットはてんかん発作が4-6週齢の限られた期間にのみ出現するという特徴を持つ。当疾患ラットで見つかった原因遺伝子は、酸化還元反応により酸化ストレスを制御する働きを持つ遺伝子のミスセンス変異である。本研究の結果、ラットの発達過程において脳の局所領域で抗酸化機能の需要が特に高まる時期があり、当疾患ラットは抗酸化活性が低下しているため発生する酸化ストレスを適切に処理しきれず細胞の障害がおき、てんかん発作につながるのではないかと推測された。

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  • けいれん重積型急性脳症モデルの確立と抗体療法の開発

    研究課題/領域番号:26670500  2014年04月 - 2017年03月

    日本学術振興会  科学研究費助成事業 挑戦的萌芽研究  挑戦的萌芽研究

    大守 伊織, 真下 知士, 大内田 守

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    配分額:3250000円 ( 直接経費:2500000円 、 間接経費:750000円 )

    けいれん重積型急性脳症モデル動物の作製を試みた。高体温誘発けいれん感受性が高く、人では急性脳症の合併が報告されているSCN1A遺伝子変異を持つラットを使用した。Scn1a遺伝子変異ラットに様々な条件でけいれん誘発を行い、あるいは炎症薬剤投与による誘発を行った。けいれんは誘発されるものの、人で特徴的な30分以上継続するような遷延性けいれんは誘発されなかった。けいれん誘発後、各種行動テストと脳組織検査を行った。空間認知障害や運動障害の合併はなかった。また、脳組織検査では、脳浮腫などの所見は認められなかった。

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  • チャネル病における発達障害の新規治療法の開発

    研究課題/領域番号:23659522  2011年 - 2012年

    日本学術振興会  科学研究費助成事業 挑戦的萌芽研究  挑戦的萌芽研究

    大守 伊織

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    配分額:3510000円 ( 直接経費:2700000円 、 間接経費:810000円 )

    発達障害には、精神遅滞、自閉症、学習障害、注意欠陥多動性障害などが含まれる。記憶や学習、情動をつかさどるシナプスの発達や可塑性、神経伝達物質の放出に関わる分子など、シナプス機能の恒常性に関わる分子が原因として注目されている。本研究課題では、神経細胞の興奮にかかわるチャネル遺伝子の異常によっても発達障害を発症し、これはてんかん発作の二次的障害や抗てんかん薬の副作用ではないことを明らかにした。

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  • 熱性痙攣の発症分子機構の解明と新規治療法の開発

    研究課題/領域番号:22591130  2010年 - 2012年

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    井上 拓志, 大守 伊織

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    配分額:4420000円 ( 直接経費:3400000円 、 間接経費:1020000円 )

    神経細胞の興奮に関わる電位依存性ナトリウムチャネルSCN1A遺伝子変異があると、熱性けいれんが起こりやすくなる。この遺伝子に変異を持つ熱性けいれんのモデルラットを用いて、熱性けいれんの発症機序の解明と新規治療法の開発を目指した。 モデルラットでは、熱性けいれん発生時に呼吸性アルカローシスになっており、10%に二酸化炭素吸入による血液ガスの補正により、熱性けいれんの持続時間は著明に短縮された。

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  • チャネル遺伝子変異をもつてんかん患者の難治化要因の解明

    研究課題/領域番号:21390312  2009年 - 2011年

    日本学術振興会  科学研究費助成事業 基盤研究(B)  基盤研究(B)

    大守 伊織, 大内田 守, 真下 知士

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    配分額:17160000円 ( 直接経費:13200000円 、 間接経費:3960000円 )

    難治てんかんの一種である乳児重症ミオクロニーてんかん(ドラベ症候群)は電位依存性ナトリウムチャネルSCN1A遺伝子変異によって発症する。本疾患の修飾因子を検索するため、患者48例に対し、電位依存性カルシウムチャネルCACNA1A遺伝子解析を行った。CACNA1A遺伝子変異/多型を21例に認め、これらの変異/多型のチャネルは機能獲得型の変化を示した。2種類のチャネル変異をもつ動物(ラット)のてんかんの症状を比較すると、1種類の変化をもつ動物よりも重症化が認められた。

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  • てんかん発症に関連する変異型ナトリウムチャネルの機能喪失機序の解明

    研究課題/領域番号:18591154  2006年 - 2008年

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    大守 伊織, 松井 秀樹, 大内田 守

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    配分額:3850000円 ( 直接経費:3400000円 、 間接経費:450000円 )

    難治てんかんの一種である乳児重症ミオクロニーてんかんに認められる電位依存性ナトリウムチャネル・1サブユニット(Na_v1.1)をコードするSCN1A遺伝子変異をもとに、その機能喪失メカニズムを解明した。変異の種類により、蛋白は合成されているが細胞膜へ移行できない障害とチャネル蛋白は膜に移行してきているがナトリウムイオンを透過することができない障害があることが推測された。蛋白が細胞膜へ移行できないある種の変異については、抗てんかん薬によって膜への移行が促進されることが分かった。これらの知見は、てんかん患者の遺伝子情報から、効果の高い治療薬を選択するテーラーメイド治療の開発に資することができると思われる。

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  • 脳内ホルモンによる情動行動の調節とその分子機構

    研究課題/領域番号:18020020  2006年 - 2007年

    日本学術振興会  科学研究費助成事業 特定領域研究  特定領域研究

    松井 秀樹, 大守 伊織

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    配分額:6200000円 ( 直接経費:6200000円 )

    研究目的
    オキシトシン受容体は海馬および扁挑体に豊富に存在し、これら領域における生理作用について注目されている。近年オキシトシンは妊娠・出産時に抗不安作用を有することが動物実験で明らかにされているが、その分子機構については不明である。本研究では、オキシトシンによる抗不安作用の分子メカニズムの解明をする。
    成果
    本研究により以下のことを明らかにした。
    1.オキシトシン添加神経培養細胞ならびに授乳中の母親マウスの脳よりmRNAを抽出し、DNA microarray法により、両者ともに発現が促進されている遺伝子を検索した。結果:両者において発現が増加している遺伝子として7個同定した。その中でもRegulator of G-rprotein signaling2 (Rgs2) の発現が最も促進していた。
    2.バージンマウスに4時聞の拘束ストレスを与え、同マウス扁桃体におけるRgs2 mRNAならびに蛋白質の発現をwestern blotting法、real time PCR法で検討した。結果:拘束1日目よりRgs2の発現が非拘束マウスと比較して有意に亢進していた。このRgs2の高い発現は拘束後1週間持続した。
    3.扁桃体を含む脳スライスにオキシトシンを潅流し、扁桃体におけるRgs2の発現をwestern blotting法にて検討した。結果:潅流30分後よりRgs2の発現が完進していた。
    4.産後授乳中母親マウスでは、バージンマウスと比較して産後3日後には著明なRgs2発現の亢進が見られた。一方産後授乳を行っていないマウスのRgs2発現は、授乳マウスと比較して明らかな発現減少が見られた。すなわち、授乳によりRgs2の発現が増加することを証明した。
    5.オキシトシン受容体のアンタゴニストをマウス扁桃体に注入し、その後拘講ストレスを与え、Rgs2の発現について検討した。結果:予備実験では、同アンタゴニストを注射したマウスでは、Rgs2の発現がコントロール群と比較して低下していた。
    6.以上より、マウスの妊娠・出産→オキシトシンの分泌増加→扁桃体におけるRgs2の発現が増加→抗不安作用という仮説を証明しつつある。

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  • オキシトシンによる扁桃体機能のモジュレーションと情動の制御

    研究課題/領域番号:17300127  2005年 - 2006年

    日本学術振興会  科学研究費助成事業 基盤研究(B)  基盤研究(B)

    松井 秀樹, 富澤 一仁, 大守 伊織, 西木 禎一, 松下 正之

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    配分額:15100000円 ( 直接経費:15100000円 )

    近年、脳内ホルモンの未知の生理作用が大きな脚光を浴びている。オキシトシンは出産、授乳時に子宮収縮や射乳を促すホルモンとして知られている。一方、同ホルモンについては脳内特に辺縁系にも多数のオキシトシン受容体が発現しており、オキシトシンの脳内における働きが注目されている。
    我々は海馬におけるオキシトシンの作用に注目して解析を行い、授乳中の母親マウスではオキシトシンにより記憶学習能力が向上することをすでに報告している。一方、近年オキシトシンによる不安情動調節作用が報告され注目されているが、そのメカニズムについては不明な点が多い。
    この基盤研究Bでは扁桃体機能に注目し、不安情動の調節機構を検索した。マウスを閉所に強制的に長時間閉じ込めるストレス負荷を行い行動解析すると、約一週間程度でストレス耐性を獲得する。この耐性獲得機構が扁桃体ニューロンにおいて、オキシトシンの分泌とRgs2と呼ばれるシグナル伝達系を介して制御されているとの仮説を証明した。
    本研究で得られた成果を今後さらに発展させ、in vivoで扁桃体へのRgs2遺伝子トランスフェクションやRNAiによる発現抑制などを行い、行動学的解析も用いて抗不安、抗ストレス作用の機構の解明を行う研究につなげてゆく予定である。
    今後この研究の発展により不安情動の新しい制御機構が可能となり、新しい治療法開発への糸口が開かれることと期待される。この意味でも本研究は大きな成果を上げることが出来た。

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  • 乳児重症ミオクロニーてんかんの早期診断と病態解明に関する分子生物学的研究

    研究課題/領域番号:16591030  2004年 - 2006年

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    大塚 頌子, 大守 伊織, 荻野 竜也

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    配分額:3200000円 ( 直接経費:3200000円 )

    乳児重症ミオクロニーてんかん(SMEDの病態生理を明らかにし、早期診断の手がかりを得るために、(1)SMEIにおける変異遺伝子の検索と変異遺伝子イオンチャネルの機能解析、(2)乳児期発症の熱性けいれんの既往をもつ症例の臨床的・分子遺伝学的研究の2つの研究を行った。(1)では、SMEIにおけるSCN1A遺伝子の変異検索とその変異イオンチャネルの活性変化をパッチクランプ法により解析した。SMEIの80.5%(33/41例)において変異が検出された。イオン選択性を担う重要なボア領域を形成するS5-S6loop領域には21.2%(7/33例)の割合で変異を検出した。パッチクランプ法による変異遺伝子の機能解析の結果、ボア領域に存在するR931C変異については電気生理学的解析により、機能喪失型変異であることが判明した。機能喪失の機序はイオン選沢性の障害と推測された。(2)では、SMEIの早期診断の手がかりを得るために、乳児期廃症の熱性けいれんまたは入浴時けいれんの既往を持ち、SMEIでないことが明らかになった3歳以上の50例について、臨床症状とSCNIA遺伝子変異の解析を行った。50例中熱性けいれんのみの症例が22例、熱性けいれんまたは入浴時けいれんと無熱時発作の合併26例、熱性けいれんとローランドてんかんの合併2例であった。SCN1A遺伝子解析の結果、50例中計6例(12%)にmissense変異を認めた。変異のあった6例はすべて熱性けいれんまたは入浴時けいれんと無熱時発作を合併していた。熱性けいれんと無熱時発作を合併する症例に限ると28例中6例(21.4%)に変異が認められた。6例の共通点は、発熱時と入浴時に発作が誘発されやすい、てんかん重積状態を認める、複雑部分発作を合併する、けいれんの家族歴がある点であった。1例を除き、片側けいれんも見られた。全例発達正常であった。この中にはGEFS+に属する症例、GEFS+に近い病像を示すが、優性遺伝がはっきりしない症例などが含まれていた。発作症状にはSMEIと類似点が多かった。

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  • 乳児重症ミオクロニーてんかんにて検出される変異型イオンチャネル遺伝子の機能解析

    研究課題/領域番号:15591110  2003年 - 2004年

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    大内田 守, 大守 伊織

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    配分額:3500000円 ( 直接経費:3500000円 )

    乳児重症ミオクロニーてんかん(severe myoclonic epilepsy in infancy ; SMEI)は生後4-6ヶ月から熱性けいれんや種々のてんかん発作が出現する難治てんかん症候群のひとつである。我々はこの疾患の原因遺伝子の検索を目的とした遺伝子解析を行った結果、ナトリウムイオンチャネル遺伝子SCN1Aのアミノ酸変異を伴う遺伝子変異を検出した。このSCN1A遺伝子変異はSMEI患者において非常に高い相関が見られることより、これらのSCN1A遺伝子変異がSMEIの発症に重要な役割を担っていると考えられた。
    そこで、変異型イオンチャネル蛋白の解析を行うことによりこれらの遺伝子変異がイオンチャネルの機能にどのような影響をもたらしているのかを明らかにする目的の為に、変異型および正常型遺伝子のSCN1A cDNAをクローニングし発現ベクターの構築を計画した。容易に蛋白局在が検出でき、蛋白機能に影響を与えず、かつ、膜への移行をさまたげないようなTagとしてLumio Tagを選び、その融合蛋白発現系を作成することにした。これは6アミノ酸からなり、特殊な蛍光物質と結合し強い蛍光を発するようになる領域である。まずこれらを正常型、変異型のC末に取り付けた発現ベクターを作成し、SCN1A遺伝子を発現していないヒト細胞株HEK293に導入した。生きたままの細胞に蛍光試薬を添加し蛍光顕微鏡で観察したところ、バックグラウンドの蛍光が非常に強く、局在を同定するのは困難であった。そこで、細胞固定後、界面活性剤処理を施した後に蛍光試薬を添加したところ、バックグラウンドの改善がみられ、ある種の変異型蛋白は細胞膜に局在することが判明した。この結果は抗SCN1A抗体を用いた免疫染色によっても確認された。このことは、正常蛋白と変異型が共発現している状態でも、変異型がDominant Negative効果により、細胞膜上で正常型の機能を阻害している可能性を示唆している。
    また、cDNAを回収する過程で、ヒトの脳組織ではSCN1A遺伝子のIsoformが複数存在することを発見した。そこで、そのIsoformの解析を行ったところ、これらはエキソン11に、11アミノ酸および28アミノ酸の欠失を持つタイプであることを明らかにした。この領域はゲートを構成するドメインIとIIの間にある細胞内ループ領域であり、そこは高頻度で変異が見つかっている領域であることより、これらのIsoformもイオンチャネルの機能に影響を及ぼすのではないかと考えられた。

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    役割:講師

    岡山県教育庁  2020年7月23日

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    種別:資格認定講習

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