Faculty Profiles - TAKEMOTO Mami

Papers - TAKEMOTO Mami

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Dynamic changes and mislocalizations of neurodegenerative disease-related proteins in mice stroke model

Xia Liu, Toru Yamashita, Xiaowen Shi, Yuting Bian, Zhihong Bian, Yoshio Omote, Mami Takemoto, Nozomi Hishikawa, Yasuyuki Ohta, Koji Abe

BRAIN RESEARCH 1742 ( 1 ) 146862 2020.9

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER

The aggregation and cellular mislocalization of several RNA-binding proteins (RBPs) have been identified as the major hallmarks of neurodegenerative diseases such as frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). However, it remains obscure whether these pathological changes also occur during cerebral ischemia. In this study, we report that RBPs increased significantly compared with the sham group (*p < 0.05 and **p < 0.01 vs sham), with nuclear depletion and cytoplasmic deposition in neurons in the acute phase of cerebral ischemia. On the other hand, such nucleocytoplasmic mislocalization were not observed in astrocytes. We provide evidence of the alteration of these neurodegeneration-related RBPs after cerebral ischemia, suggesting a potential association between cerebral ischemia and neurodegenerative diseases.

DOI： 10.1016/j.brainres.2020.146862

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A unique leukoencephalopathy accompanied by palmoplantar pustulosis with identical pathological feature of helper T cell accumulation.

Sasaki R, Omote Y, Tadokoro K, Matsumoto N, Nomura E, Takemoto M, Hishikawa N, Yamashita T, Ohta Y, and Abe K

Neurology Asia 25 ( 3 ) 415 - 418 2020.9

脳卒中マウスモデルにおけるTocotrienol製剤前投与の治療効果

山下徹, 商敬偉, 馮田, 武本麻美, 菱川望, 太田康之, 阿部康二

日本抗加齢医学会総会プログラム・抄録集 20回 224 - 224 2020.9

Improvement of a decreased anti-oxidative activity by edaravone in amyotrophic lateral sclerosis patients

Yasuyuki Ohta, Toru Yamashita, Emi Nomura, Nozomi Hishikawa, Ken Ikegami, Yosuke Osakada, Namiko Matsumoto, Yuko Kawahara, Taijun Yunoki, Yoshiaki Takahashi, Motonori Takamiya, Koh Tadokoro, Ryo Sasaki, Yumiko Nakano, Keiichiro Tsunoda, Kota Sato, Yoshio Omote, Mami Takemoto, Koji Abe

JOURNAL OF THE NEUROLOGICAL SCIENCES 415 ( 15 ) 116906 2020.8

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER

Background: The free radical scavenger edaravone is a proven neuroprotective drug for patients with amyotrophic lateral sclerosis (ALS). Our objective was to evaluate the therapeutic effects of edaravone for oxidative stress and anti-oxidative activity in ALS patients.Methods: Twenty-two ALS patients with a disease duration of 2 years, treated by edaravone, and 25 control participants were evaluated according to their clinical scores, including ALS functional rating scale-revised (ALSFRS-R), and serum and cerebrospinal fluid (CSF) markers of oxidative stress dROM and anti-oxidative activity OXY.Results: Serum and CSF markers of anti-oxidative activity OXY were significantly decreased in ALS patients at pre-treatment compared with controls ((##)p < .01), which was improved in the course of edaravone treatment. Both serum and CSF OXY were significantly correlated with ALS clinical scores including ALSFRS-R (*p < .05, **p < .01, ***p < .001). Furthermore, serum OXY at pre-treatment was significantly correlated with a change in the ALSFRS-R score in the sixth cycle of edaravone treatment (*p < .05).Conclusions: The present study suggests significant correlations between anti-oxidative activity and ALS clinical severity, and the therapeutic efficacy of edaravone for decreased anti-oxidative activity in ALS.

DOI： 10.1016/j.jns.2020.116906

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Antioxidative effects of a novel dietary supplement Neumentix in a mouse stroke model. International journal

Yuki Taira, Toru Yamashita, Yuting Bian, Jingwei Shang, Namiko Matsumoto, Ryo Sasaki, Koh Tadokoro, Emi Nomura, Keiichiro Tsunoda, Yoshio Omote, Mami Takemoto, Nozomi Hishikawa, Yasuyuki Ohta, Koji Abe

Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association 29 ( 8 ) 104818 - 104818 2020.8

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: During an acute stroke, reactive oxygen species are overproduced and the endogenous antioxidative defense systems are disrupted. Therefore, antioxidative therapy can be a promising scheme to reduce the severity of stroke. Neumentix is a novel antioxidative supplement produced from a patented mint line and contains a high content of rosmarinic acid (RA). Although Neumentix has proven diverse efficacy and safety in clinical trials, its effect on strokes is unclear. METHODS: Mice that were treated with Neumentix or vehicle for 14 days underwent transient middle cerebral artery occlusion (tMCAO) for 60 min. Mice were sacrificed 5 days after tMCAO. RESULTS: Neumentix preserved body weight after tMCAO, showed a high antioxidative effect in serum, and reduced infarction volume compared to the vehicle. The expression of 4-hydroxy-2-nonenal, Nε-(carboxymethyl) lysine, and 8-hydroxy-2'-deoxyguanosine was reduced in Neumentix-treated mice. CONCLUSION: The antioxidative effect of Neumentix was confirmed. This is the first report to demonstrate the antioxidative effect of Neumentix on strokes.

DOI： 10.1016/j.jstrokecerebrovasdis.2020.104818

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PDDとDLBの認知機能と情動機能、脳血流画像の比較

武本麻美, 田所功, 表芳夫, 菱川望, 太田康之, 山下徹, 阿部康二

日本老年医学会雑誌 57 ( Suppl. ) 111 - 112 2020.7

Up-regulation of sphingosine-1-phosphate receptors and sphingosine kinase 1 in the peri-ischemic area after transient middle cerebral artery occlusion in mice

Namiko Matsumoto, Toru Yamashita, Jingwei Shang, Tian Feng, Yosuke Osakada, Ryo Sasaki, Koh Tadokoro, Emi Nomura, Keiichiro Tsunoda, Yoshio Omote, Mami Takemoto, Nozomi Hishikawa, Yasuyuki Ohta, Koji Abe

BRAIN RESEARCH 1739 ( 15 ) 146831 2020.7

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER

There is thought to be a strong relationship between sphingosine-1-phosphate (S1P) signaling and pathophysiolosy of cerebral ischemia. We examined the change of expression and distribution of SIP receptors (S1PRs) and sphingosine kinases (SphKs) after cerebral ischemia in male C57BL6/J mice using immunohistochemical analysis at 1, 5, 14, and 28 days after 30 min of transient middle cerebral artery occlusion (tMCAO). S1PR1, 3, and 5 were transiently induced in the cells, which were morphologically similar to neurons in the pert-infarct lesion with a peak seen at 1 day after tMCAO (p < 0.01 vs. sham control). S1PR2 appeared in the inner layer of vessels in the ischemic core (p < 0.01 vs. sham control) and the pert-infarct lesion (p < 0.01 vs. sham control) at the acute phase after tMCAO. However, SphK1 was strongly induced at 1 and 5 days after tMCAO (p < 0.01 vs. sham control) in the peri-infarct lesion, whereas SphK2 expression did not change. Western blot analysis at 1 and 5 days after 30 min of tMCAO revealed that the expression of S1PRs were transiently enhanced at the acute phase, which was consistent with the immunohistochemical results. Double immunofluorescent analysis revealed S1PR2/NG2- and S1PR2/CD31-, S1PR3/CD31-, and S1PR5/CD31-double positive cells in the peri-infarct lesion 1 day after tMCAO. The present results suggest that S1PRs and SphK1 may be important therapeutic targets for rescuing the pert-infarct lesion.

DOI： 10.1016/j.brainres.2020.146831

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Adult-onset frequent non-convulsive status epilepticus in a patient with ring chromosome 20 syndrome

Xia Liu, Yoshio Omote, Ken Ikegami, Koh Tadokoro, Mami Takemoto, Nozomi Hishikawa, Toru Yamashita, Yasuyuki Ohta, Koji Abe

NEUROLOGY AND CLINICAL NEUROSCIENCE 8 ( 4 ) 202 - 204 2020.7

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY

We report a 31-year-old woman with ring chromosome 20 syndrome who presented with epilepsy staring from 16 years old and loss of consciousness from 30 years old. Her neurological examinations and psychological testing were normal, without dysmorphic features. No abnormalities were found in neuroimaging. Electroencephalogram recording showed typical non-convulsive status epilepticus associated with alteration of consciousness. Her diagnosis was based on the cytogenetic analysis indicating that her karyotype was 46, XX, r(20)(p13q13.3)[9]/46, XX[21]. She had refractory epilepsy and improved by a combination of valproate and lacosamide.

DOI： 10.1111/ncn3.12389

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Familial dropped head syndrome with extremity muscle weakness

Keiichiro Tsunoda, Nozomi Hishikawa, Yoshio Omote, Ken Ikegami, Yumiko Nakano, Kota Sato, Mami Takemoto, Yasuyuki Ohta, Toru Yamashita, Koji Abe

NEUROLOGY AND CLINICAL NEUROSCIENCE 8 ( 4 ) 189 - 191 2020.7

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY

We report a new case of familial dropped head syndrome (DHS) due to myopathy. The proband is a 63-year-old woman, and her younger sister and son also showed DHS. She was not good at sport since elementary school and showed unique muscle weakness in her paraspine and four limbs. A blood test showed a slight increase in creatine kinase (237 IU/mL) and myoglobin (95 ng/mL). An electromyogram showed myogenic change, and computed tomography revealed a normal muscle volume of the neck but paraspinal muscle atrophy. Muscle biopsy of the right femoral muscle found type 2 fiber atrophy. Based on these unique clinical features, this is the first report of familial DHS which probably due to congenital myopathy.

DOI： 10.1111/ncn3.12382

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抗酸化サプリメントTwendee Xの軽度認知障害に対する効果についての検討

松本菜見子, 田所功, 森原隆太, 太田康之, 菱川望, 川野公子, 武本麻美, 山下徹, 犬房春彦, 阿部康二

日本老年医学会雑誌 57 ( Suppl. ) 113 - 113 2020.7

PDDとDLBの認知機能と情動機能、脳血流画像の比較

武本麻美, 田所功, 表芳夫, 菱川望, 太田康之, 山下徹, 阿部康二

日本老年医学会雑誌 57 ( Suppl. ) 111 - 112 2020.7

"もの忘れ外来"通院患者の通院脱落に関わる因子

菱川望, 表芳夫, 武本麻美, 太田康之, 山下徹, 阿部康二

日本老年医学会雑誌 57 ( Suppl. ) 112 - 112 2020.7

Bone Marrow Stromal Cell Transplantation Drives Molecular Switch from Autophagy to the Ubiquitin-Proteasome System in Ischemic Stroke Mice

Koh Tadokoro, Yusuke Fukui, Toru Yamashita, Xia Liu, Keiichiro Tsunoda, Jingwei Shang, Ryuta Morihara, Yumiko Nakano, Feng Tian, Ryo Sasaki, Namiko Matsumoto, Emi Nomura, Xiaowen Shi, Yoshio Omote, Mami Takemoto, Nozomi Hishikawa, Yasuyuki Ohta, Koji Abe

JOURNAL OF STROKE & CEREBROVASCULAR DISEASES 29 ( 5 ) 104743 2020.5

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER

Background: Bone marrow stromal cell (BMSC) transplantation is a promising therapeutic approach for cerebral ischemia, as it elicits multiple neuroprotective effects. However, it remains unclear how BMSC transplantation modulates the ubiquitin-proteasome system (UPS) and autophagy under cerebral ischemia. Methods: In the present study, an intermediate level of cerebral ischemia (30 minutes) was chosen to examine the effect of BMSC transplantation on the molecular switch regulating UPS and autophagy. BMSC or vehicle was stereotactically injected into the penumbra 15 minutes after sham operation or transient middle cerebral artery occlusion (tMCAO). Results: Thirty minutes of tMCAO artery occlusion significantly increased TUNEL-, ubiquitin-, and p62-positive cells (which peaked at 72 hours, 2 hours, and 2 hours after reperfusion, respectively) and ratios of both BAG3/BAG1 and LC3-II/LC3-I at 24 hours after reperfusion. However, intracerebral injection of BMSCs significantly reduced infarct volume and numbers of TUNEL- and p62-positive cells, and improved BAG3/BAG1 and LC3-II/LC3-I ratios. In addition, observed increases in ubiquitin-positive cells 2 hours after reperfusion were slightly suppressed by BMSC transplantation. Conclusions: These data suggest a protective role of BMSC transplantation, which drove the molecular switch from autophagy to UPS in a murine model of ischemic stroke.

DOI： 10.1016/j.jstrokecerebrovasdis.2020.104743

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Diabetic painful truncal neuropathy with hypohidrosis and facial palsy

Keiichiro Tsunoda, Yoshio Omote, Nozomi Hishikawa, Ken Ikegami, Yumiko Nakano, Kota Sato, Mami Takemoto, Yasuyuki Ohta, Toru Yamashita, Kentaro Deguchi, Koji Abe

NEUROLOGY AND CLINICAL NEUROSCIENCE 8 ( 3 ) 155 - 157 2020.5

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY

Truncal neuropathy is a rare phenotype of diabetic neuropathy. Here, we report the first case of diabetic painful truncal neuropathy complaining of back pain with hypohidrosis confirmed by a sweat test accompanied by cranial nerve palsy. The patient had poorly controlled type 2 diabetes mellitus and suffered from back pain followed by facial palsy. After pulse therapy with methylprednisolone facial palsy improved, but back pain was intractable with a loss of body weight. The sweat test showed hypohidrosis on the back and soles on his feet. Sural nerve biopsy revealed decreased small fibers and mild axonopathy. After palliative therapy, his symptoms gradually improved.

DOI： 10.1111/ncn3.12370

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A spontaneous recovery of anti-galactocerebroside antibody-associated encephalitis without evidence of Mycoplasma infection

Koh Tadokoro, Yoshio Omote, Yosuke Osakada, Ken Ikegami, Kota Sato, Mami Takemoto, Nozomi Hishikawa, Yasuyuki Ohta, Toru Yamashita, Koji Abe

NEUROLOGY AND CLINICAL NEUROSCIENCE 8 ( 3 ) 164 - 166 2020.5

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY

Anti-galactocerebroside (Gal-C) antibody is characteristic of encephalomyelitis and Guillain-Barre syndrome subsequent to mycoplasma infection. Here, we report a 75-year-old Japanese man who presented somnolence, signs of meningeal irritation, and parkinsonian features with positive serum inflammatory markers and cerebrospinal fluid (CSF) pleocytosis. Although anti-Mycoplasma pneumoniae antibody was negative, anti-Gal-C antibody was later detected in his serum. The present case recovered spontaneously without any other specific therapies.

DOI： 10.1111/ncn3.12379

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Discrepancy of subjective and objective sleep problems in Alzheimer's disease and mild cognitive impairment detected by a home-based sleep analysis

Koh Tadokoro, Yasuyuki Ohta, Nozomi Hishikawa, Emi Nomura, Yosuke Wakutani, Yoshiki Takao, Yoshio Omote, Mami Takemoto, Toru Yamashita, Koji Abe

JOURNAL OF CLINICAL NEUROSCIENCE 74 76 - 80 2020.4

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCI LTD

There is a strong relationship between Alzheimer's disease (AD) and sleep problems, and a sleep condition is informative for evaluating the AD status. In the present study, we evaluated subjective sleep problems in AD and mild cognitive impairment (MCI) with self-check questionnaires and objective sleep problems with a convenient home-based portable device, WatchPAT. A total of 63 subjects with normal cognition (NC) (n = 22), MCI (n = 20), and AD (n = 21) were cross-sectionally investigated. AD patients showed a better self-check Pittsburgh sleep quality index (PSQI) score (*p < 0.05) than NC and MCI patients. On the other hand, WatchPAT analysis showed a significantly reduced rapid eye movement (REM) sleep (*p < 0.05) and increased light sleep in AD patients (*p < 0.05) compared with NC subjects, and mildly reduced REM and increased light sleep in MCI subjects. The present study revealed a gap between the subjective self-check sleep questions and the objective WatchPAT analysis in AD patients. Thus, a home-based sleep study with WatchPAT is a useful tool to detect an objective sleep problem in AD and the risk of MCI conversion into AD. (C) 2020 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jocn.2020.01.085

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A unique case of myasthenia gravis mimicking Garcin’s syndrome.

Tadokoro K, Hishikawa N, Ikegami K, Nomura E, Kawahara Y, Omote Y, Takemoto M, Yamashita T, Abe K

Neurol Clin Neurosci 1 - 4 2020.4

Delayed Serial Microvascular Injury and Cognitive Decline After Whole Brain Irradiation.

Osakada Y, Yamashita T, Ikegami K, Kawahara Y, Omote Y, Hishikawa N, Takemoto M, Ohta Y, Abe K

Japanese Society of Vascular Cognitive Impairment 6 23 - 26 2020.4

A juvenile case of idiopathic hypertrophic pachymeningitis involved cavernous sinus and proximal trigeminal nerve

Zhihong Bian, Yoshio Omote, Koh Tadokoro, Ken Ikegami, Yosuke Osakada, Mami Takemoto, Nozomi Hishikawa, Toru Yamashita, Yasuyuki Ohta, Koji Abe

NEUROLOGY AND CLINICAL NEUROSCIENCE 8 ( 2 ) 82 - 85 2020.3

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY

Idiopathic hypertrophic pachymeningitis (HP) is a rare inflammatory disorder characterized by local or diffuse thickening of the cranial or spinal dura mater, which is primarily reported in adults. Here, we report a juvenile idiopathic HP case presenting diplopia and multiple cranial nerve palsies. Although cranial magnetic resonance imaging (MRI) shows evident lesions in cavernous sinus and preganglionic segment of trigeminal nerve, only cerebrospinal fluid (CSF) showed elevated protein (55 mg/dL) and myelin basic protein (MBP, 355 pg/mL) but negative systemic inflammatory markers. Steroid therapy greatly improved the symptom and the CSF data in 1 month.

DOI： 10.1111/ncn3.12355

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LGI1 antibody-associated limbic encephalitis started from unilateral basal ganglia to medial temporal lobe and insula

Xia Liu, Yoshio Omote, Yosuke Osakada, Koh Tadokoro, Mami Takemoto, Nozomi Hishikawa, Toru Yamashita, Yasuyuki Ohta, Koji Abe

NEUROLOGY AND CLINICAL NEUROSCIENCE 8 ( 2 ) 68 - 71 2020.3

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY

Leucine-rich glioma-inactivated 1 (LGI1) antibody-associated limbic encephalitis is a rare autoimmune encephalitis. Here, we report a 39-year-old woman presented with generalized tonic-clonic seizures, night delirium, bilateral upper limb tremor, and hyponatremia. Her symptoms did not improve with initial steroid therapy, and brain magnetic resonance imaging (MRI) showed a progression of abnormalities from right basal ganglia to medial temporal lobe and insula. The presence of LGI1 antibodies in the patient's serum confirmed the clinical diagnosis. After the combined treatments of methylprednisolone, plasma exchange, and intravenous immunoglobulin, her clinical symptoms resolved completely.

DOI： 10.1111/ncn3.12351

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