Papers - HASHIMOTO Eri

Stem cell therapy could improve social activities of FASD model rats

SHIRASAKA Tomohiro, ONO Takahumi, UKAI Wataru, YOSHINAGA Toshihiro, ISHII Takao, WATANABE Kimihiko, WATANABE Ippei, TATENO Masru, HASHIMOTO Eri, SAITO Toshikazu

日本アルコール・薬物医学会雑誌 = Japanese journal of alcohol studies & drug dependence ( (一社)日本アルコール・アディクション医学会 )  44 ( 4 ) 282 - 283  2009.08

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Comorbidity of alcoholism and depression

HASHIMOTO Eri, UKAI Wataru, SAITO Toshikazu

日本アルコール・薬物医学会雑誌 = Japanese journal of alcohol studies & drug dependence   44 ( 4 ) 226 - 227  2009.08

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アルコールによる脳神経ネットワークの変異 : 行動変化と分子メカニズムの解析から

鵜飼 渉, 橋本 恵理, 石井 貴男, 白坂 知彦, 吉永 敏弘, 館農 勝, 小野 貴文, 渡邊 公彦, 渡邉 一平, 齋藤 利和

日本アルコール・薬物医学会雑誌 = Japanese journal of alcohol studies & drug dependence   44 ( 4 ) 270 - 271  2009.08

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アルコール性障害としてのうつ病と自殺 うつ病とアルコール依存症の併存について

橋本 恵理, 鵜飼 渉, 齋藤 利和

日本アルコール・薬物医学会雑誌 ( (一社)日本アルコール・アディクション医学会 )  44 ( 4 ) 226 - 227  2009.08

アルコール・薬物関連障害の生物学的研究の動向 アルコールによる脳神経ネットワークの変異 行動変化と分子メカニズムの解析から

鵜飼 渉, 橋本 恵理, 石井 貴男, 白坂 知彦, 吉永 敏弘, 館農 勝, 小野 貴文, 渡邊 公彦, 渡邉 一平, 齋藤 利和

日本アルコール・薬物医学会雑誌 ( (一社)日本アルコール・アディクション医学会 )  44 ( 4 ) 270 - 271  2009.08

【統合失調症は神経発達障害か、神経変性疾患か】非定型抗精神病薬の神経新生作用

橋本 恵理, 鵜飼 渉, 小野 貴文, 齋藤 利和

脳21 ( (株)金芳堂 )  12 ( 2 ) 195 - 199  2009.04

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統合失調症の病態における形態学的異常の問題が明らかとなってきている。この脳形態変化を神経発達障害、進行性脳障害、治療薬による変化という三要素の複合として考えると、脳内神経ネットワークの構築・維持・修復の障害ととらえることができる。よって神経ネットワークの破壊・脱落を防ぎ、神経新生を促進する方向での取り組みが治療的に有用と思われる。非定型抗精神病薬は神経新生を促進する効果を有し、この作用を介して神経ネットワークの障害を修復し、認知機能障害の改善などの臨床効果発現に結びついている可能性がある。その作用機序としては、神経栄養因子シグナル伝達や小胞体ストレスの軽減の関与が考えられるところであるが、今後の更なる検討から、病態解明やより良い薬物療法への応用へと結びつくことが期待される。(著者抄録)

Neural network regeneration/repair and cognitive recovery in affective disorders

鵜飼 渉, 橋本 恵理, 石井 貴男

Japanese journal of clinical psychiatry ( アークメディア )  38 ( 4 ) 421 - 428  2009.04

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Neural network regeneration/repair and cognitive recovery in affective disorders

鵜飼 渉, 橋本 恵理, 石井 貴男, 吉永 敏弘, 渡邊 公彦, 小野 貴文, 館農 勝, 渡邉 一平, 白坂 智彦, 齋藤 利和

Japanese journal of clinical psychiatry ( (株)アークメディア )  38 ( 4 ) 421 - 428  2009.04

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精神疾患の脳神経回路修復 個別診断と薬物・細胞コンバインド療法の可能性の検討

鵜飼 渉, 渡邊 公彦, 吉永 敏弘, 橋本 恵理, 小野 貴文, 石井 貴男, 館農 勝, 渡邉 一平, 白坂 智彦, 齋藤 利和

精神薬療研究年報 ( (公財)先進医薬研究振興財団 )  ( 41 ) 47 - 48  2009.03

Low serum BDNF and food intake regulation: A possible new explanation of the pathophysiology of eating disorders

Satoshi Saito, Kimihiko Watanabe, Eri Hashimoto, Toshikazu Saito

PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY ( PERGAMON-ELSEVIER SCIENCE LTD )  33 ( 2 ) 312 - 316  2009.03  [Refereed]

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Background: Several lines of evidence suggest that brain-derived neurotrophic factor (BDNF) plays an important role in weight regulation and eating behavior, and poorly balanced diets lead to a decrease in blood BDNF levels. However, studies regarding BDNF blood levels in eating disorders (ED) have yielded inconsistent results. We measured serum concentrations of BDNF and assessed behavior and cognition related to eating in ED patients and control subjects. Methods: Forty female drug-free patients [19 with anorexia nervosa (AN), 21 with bulimia nervosa (BN)], who did not meet the diagnostic criteria for depressive disorder, and 24 age-matched normal control subjects were enrolled in the current study. We evaluated eating-related psychopathology and depressive symptoms using the Eating Disorder Inventory-2 (EDI-2), Eating Attitude Test-26 (EAT-26) and the Hamilton Depression Rating Scale (HDRS), and measured serum BDNF levels by an enzyme-linked immunosorbent assay. Results: Compared to normal controls, serum levels of BDNF were significantly reduced in AN, but not in BN. There was a significant positive correlation between serum BDNF levels and BMI in both AN patients (r=.649, p=.003) and BN patients (r=.626, p=.002). However, no correlation between serum BDNF levels and BMI was detected in the controls. Furthermore, there was a significant negative correlation between serum BDNF levels and the oral control subscale scores of EAT in both AN patients (r=-.506, p=.027) and BN patients (r=-.511, p=.018); whereas, no correlation was detected in normal controls. Conclusion: Our study demonstrated that individuals showing more extreme food intake regulation were those with lower serum BDNF levels. This finding is contrary to that in mice where mice with reduced BDNF levels showed aberrant eating behavior. This result suggests that BDNF is no longer functioning appropriately in ED patients, which could be an important factor in the pathophysiological of ED. (C) 2008 Elsevier Inc. All rights reserved.

DOI PubMed

The analysis of impairment and repair of neural network by ethanol : In vitro and in vivo studies using neurons and neural stem cells

UKAI Wataru, ISHII Takao, YOSHINAGA Toshihiro, TATENO Masaru, HASHIMOTO Eri, ONO Takafumi, WATANABE Kimihiko, WATANABE Ippei, SHIRASAKA Tomohiro, SAITO Toshikazu

日本アルコール・薬物医学会雑誌 = Japanese journal of alcohol studies & drug dependence ( (一社)日本アルコール・アディクション医学会 )  43 ( 6 ) 763 - 769  2008.12  [Domestic journal]

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Recent clinical neuroimaging studies have suggested the morphological brain changes occur and progress in the course of alcoholism and depression. The abnormality of neurogenesis has emerged as a potential epidemiological mechanism of these diseases. Previously, we have indicated the low dose of ethanol that could not influence on the survival of neurons and neural stem cell (NSC) suppress differentiation to neurons but glias through activation of neuron-restrictive silencing factor/repressor element-1 silencing transcription factor (NRSF/REST). We revealed the endoplasmic reticulum function and trophic factor signaling change implicated in this mechanism of ethanol action on NSC differentiation change. The analysis of potentials of psychotropic drugs on the ethanol-induced NSC function change may reveal the possible biological way of neural network impairment and its repair. Furthermore, the approach of using stem cells such as intravenous NSC transplantation can be a useful method to clarify the neural network reconstruction damaged by ethanol. The importance of interactive analysis of in vitro to in vivo should be documented for the pathophysiological understanding and new therapy development against alcohol-induced brain damage.

PubMed CiNii

ヒト前前頭皮質におけるニューロン及び非ニューロン核のDNAメチル化解析 プロモータータイリングアレイ解析(DNA methylation analysis of neuronal and non-neuronal nuclei in the human prefrontal cortex: promoter tiling array analysis)

岩本 和也, 文東 美紀, 上田 順子, 中野 陽子, 鵜飼 渉, 橋本 恵理, 齋藤 利和, 加藤 忠史

日本生化学会大会・日本分子生物学会年会合同大会講演要旨集 ( (公社)日本生化学会 )  81回・31回   3T22 - 8  2008.11

Epigenetic regulation in alcohol-related brain damage

ISHII Takao, HASHIMOTO Eri, UKAI Wataru, TATENO Masaru, YOSHINAGA Toshihiro, ONO Takahumi, WATANABE Kimihiko, SAITO Satoshi, SAITO Toshikazu

日本アルコール・薬物医学会雑誌 = Japanese journal of alcohol studies & drug dependence ( (一社)日本アルコール・アディクション医学会 )  43 ( 5 ) 705 - 713  2008.10

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Protective effects of psychotropic drugs on endoplasmic reticulum (ER) stress in psychiatric disorders

Toshikazu Saito, Wataru Ukai, Toshihiro Yoshinaga, Takao Ishii, Takafumi Ono, Kimihiko Watanabe, Eri Hashimoto

JOURNAL OF NEURAL TRANSMISSION ( SPRINGER WIEN )  115 ( 10 ) 1474 - 1474  2008.10  [Refereed]

Neuroprotective effects of Yi-Gan San against beta amyloid-induced cytotoxicity on rat cortical neurons

Masaru Tateno, Wataru Ukai, Takafumi Ono, Satoshi Saito, Ed Hashimoto, Toshikazu Saito

PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY ( PERGAMON-ELSEVIER SCIENCE LTD )  32 ( 7 ) 1704 - 1707  2008.10  [Refereed]

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Introduction: Recent clinical studies have demonstrated that Yi-Gan San (YGS, Yokukan-San in Japanese), a Chinese herbal medicine, alleviates various dementia-related symptoms. However, Chinese herbal medicines have rarely been investigated scientifically and the underlying mechanism of YGS remains uncertain. In this study, we investigated the effect of YGS on beta amyloid protein (A beta)-induced cytotoxicity in a primary culture of rat cortical neurons. Methods: Cortical neurons prepared from rat embryos were exposed to A beta in the presence or absence of YGS. The protective effect of YGS was measured as the % of control (unexposed neurons) by using MTT assay and LDH assay. Results: A beta significantly decreased the number of surviving cortical neurons at a dose of 20 mu M and higher. In the presence of 20 mu M A beta, YGS concentrations of 10(-5) g/L (W/V) and higher significantly increased the number of viable neurons. Conclusion: Our study demonstrated a neuroprotective effect of Yi-Gan San against AB-induced cytotoxicity. Since according to traditional herbal medicine beliefs, YGS most likely exerts its clinical effects not through a single constituent but as a mixture of several herbal ingredients, the true mechanism of this neuroprotective action remains unclear. However, our results suggest that this Chinese herbal medicine might be a valuable treatment for clinical symptoms associated with dementia having fewer side effects and possible additional neuroprotective effects in the elderly. (c) 2008 Elsevier Inc. All rights reserved.

DOI PubMed

Current drug development on the prospect for advanced therapy of schizophrenia

WATARU Ukai, HASHIMOTO Rie, SAITO Toshikazu

脳と精神の医学 = Brain science and mental disorders   19 ( 3 ) 173 - 179  2008.09

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Lithium-induced suppression of transcription repressor NRSF/REST: Effects on the dysfunction of neuronal differentiation by ethanol

Takao Ishii, Eri Hashimoto, Wataru Ukai, Masaru Tateno, Toshihiro Yoshinaga, Satoshi Saito, Hitoshi Sohma, Toshikazu Saito

EUROPEAN JOURNAL OF PHARMACOLOGY ( ELSEVIER SCIENCE BV )  593 ( 1-3 ) 36 - 43  2008.09  [Refereed]

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Lithium, a mood-stabilizing drug, is widely used to treat bipolar affective disorder. Recent studies have demonstrated that lithium has neuroprotective and neurotrophic properties, which may relate to its clinical effectiveness. Ethanol is a deleterious agent that causes various kinds of neuronal damage to both the developing and adult brain. In this study, we investigated the potential of lithium to produce recovery of ethanol-induced suppressed neuronal differentiation at ethanol concentrations lower than those that affect the viability of neural stem cells (NSCs). We evaluated the effect of lithium on neuronal differentiation of NSCs obtained from rat embryos. To elucidate the molecular mechanisms underlying the altered neuronal differentiation induced by lithium and ethanol, we focused on neuron-restrictive silencer factor (NRSF), which represses transcription of neuronal genes in the terminal stage of NSC differentiation. Lithium increased neuronal differentiation and decreased ethanol-induced suppression of neuronal differentiation of NSCs. Furthermore, lithium reduced the DNA binding activity and protein level of NRSF enhanced by ethanol. Based on our findings, we speculate that lithium may be efficacious in the treatment of ethanol-induced neurological deficits. (C) 2008 Elsevier B.V. All rights reserved.

DOI PubMed

The alteration of CREB/NRSF regulation in the neural stem cell dysfunction by ethanol

UKAI Wataru, ISHII Takao, HASHIMOTO Eri, YOSHINAGA Toshihiro, TATENO Masaru, ONO Takafumi, WATANABE Kimihiko, WATANABE Ippei, SHIRASAKA Tomohiro, SAITO Satoshi, SAITO Toshikazu

日本アルコール・薬物医学会雑誌 = Japanese journal of alcohol studies & drug dependence ( (一社)日本アルコール・アディクション医学会 )  43 ( 4 ) 574 - 575  2008.08

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【神経新生と病態】薬物と神経新生 向精神薬

橋本 恵理, 小野 貴文, 渡邊 公彦

Clinical Neuroscience ( (株)中外医学社 )  26 ( 8 ) 887 - 889  2008.08

The neural network abnormalities by alcohol: Approach for repair using neural stem cells

Wataru Ukai, Eri Hashimoto, Toshihiro Yoshinaga, Takao Ishii, Masaru Tateno, Takafumi Ono, Kimihiko Watanabe, Satoshi Saito, Toshikazu Saito

Japanese Journal of Neuropsychopharmacology   28 ( 2 ) 69 - 73  2008.04  [Refereed]

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Recent clinical neuroimaging studies have revealed the possible relation between morphological brain changes, and memory, cognitive impairment in the course of alcoholism and depression. In the previous studies, we have been analyzing the mechanism of neural network disruption by ethanol using postmortem human brain and cultured cells, and identified the sensitive effect of ethanol on the neural stem cell (NSC) differentiation rather than the influence on neuronal cell survival. Furthermore, to develop a novel method for reconstruction of the neural network damaged by ethanol, we tried to analyze the usefulness of intravenous NSC transplantation in fetal alcohol syndrome spectrum disorder (FASD) model rats. In the in vitro studies, we have found the suppressive effect of ethanol on NSC differentiation to neurons, through alteration of transcription factor, CREB and NRSF/REST activities, by the cellular signaling cascade changes including trophic factors and endoplasmic reticulum (ER) function. In the in vivo studies, we have shown the effective migration of labeled NSCs into the brain of FASD model rats, and revealed the therapeutic potential of this transplantation for the treatment of anxiety/cognitive dysfunction and behavioral abnormalities in alcohol-induced brain neural network damage. We are going to the next step for analysis of transplanted NSC dynamics in the brain, which must play a pivotal role in the effective induction of behavioral recoveries.

PubMed