Details of a Researcher - HASHIMOTO Eri

Papers - HASHIMOTO Eri

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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 ( (一社)日本神経精神薬理学会 ) 28 ( 2 ) 69 - 73 2008.04

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 CiNii

老年痴呆における情報伝達系の変化

橋本恵理, 山本恵, 齋藤利和, 高畑直彦

老年期痴呆研究会誌 ( 老年期認知症研究会 ) 14 6 - 8 2007.12

Detection of Chromosomal Structural Alterations in Single Cells by SNP Arrays: A Systematic Survey of Amplification Bias and Optimized Workflow

Kazuya Iwamoto, Miki Bundo, Junko Ueda, Yoko Nakano, Wataru Ukai, Eri Hashimoto, Toshikazu Saito, Tadafumi Kato

PLOS ONE ( PUBLIC LIBRARY SCIENCE ) 2 ( 12 ) e1306 2007.12 [Refereed]

Background. In single-cell human genome analysis using whole-genome amplified product, a strong amplification bias involving allele dropout and preferential amplification hampers the quality of results. Using an oligonucleotide single nucleotide polymorphism (SNP) array, we systematically examined the nature of this amplification bias, including frequency, degree, and preference for genomic location, and we assessed the effects of this amplification bias on subsequent genotype and chromosomal copy number analyses. Methodology/Principal Findings. We found a large variability in amplification bias among the amplified products obtained by multiple displacement amplification (MDA), and this bias had a severe effect on the genotype and chromosomal copy number analyses. We established optimal experimental conditions for pre-screening for high-quality amplified products, processing array data, and analyzing chromosomal structural alterations. Using this optimized protocol, we successfully detected previously unidentified chromosomal structural alterations in single cells from a lymphoblastoid cell line. These alterations were subsequently confirmed by karyotype analysis. In addition, we successfully obtained reproducible chromosomal copy number profiles of single cells from the cell line with a complex karyotype, indicating the applicability and potential of our optimized workflow. Conclusions/Significance. Our results suggest that the quality of amplification products should be critically assessed before using them for genomic analyses. The method of MDA-based whole-genome amplification followed by SNP array analysis described here will be useful for exploring chromosomal alterations in single cells.

DOI PubMed

Case reports: Three cases of schizophrenia in Japanese studying abroad

細田さくら, 山川友子, 橋本恵理

Psychiatry ( (有)科学評論社 ) 11 ( 5 ) 399 - 404 2007.11

海外留学中に幻覚妄想状態を呈した後、統合失調症と診断された3例を報告し、海外留学と統合失調症性の関連性と鑑別診断について考察した。海外渡航等重大な環境変化後に幻覚・妄想状態を呈する症例の中には、一見、短期反応性精神病等の反応性の精神障害に思われるが、症状と経過を厳密に観察すると、幻覚・妄想の特徴や、幻覚・妄想が消失した後に無為自閉、感情の平板化、意欲・集中力の低下などの残遺症状、統合失調症と診断される症例もあるため、慎重な鑑別およびその後のフォローアップが必要である。急性期の後には、統合失調症に対する薬物療法だけでなく、望んで行った海外留学を断念せざるを得なかった精神的ショックに対して支持的な精神療法も必要となってくる。

CiNii

Case reports: Three cases of schizophrenia in Japanese studying abroad

細田さくら, 山川友子, 橋本恵理

Psychiatry ( 科学評論社 ) 11 ( 5 ) 399 - 404 2007.11

CiNii

【各科臨床でみられる抑うつの診断と治療】アルコール使用障害とうつ病の併存(comorbidity)

齋藤諭, 橋本恵理, 齋藤利和

クリニカ ( (株)トプコ出版部 ) 34 ( 5 ) 270 - 272 2007.09

アルコール依存やアルコール乱用とうつ病のcomorbidityは非常に高率である。両疾患が併存した場合に自殺の危険性が高まるため、飲酒習慣を持つ者に抑うつ症状を認めた際には、アルコールの問題を見落とさないように注意することが必要である。アルコール依存に併存するうつ症状は、断酒をすることのみで改善する場合もある。しかし、断酒には飲酒行動の背景にある葛藤状態に対する精神療法が重要となる。(著者抄録)

エタノールによる神経幹細胞の分化制御小胞体機能に関わる分子変動の解析

石井貴男, 鵜飼渉, 館農勝, 吉永敏弘, 小野貴文, 渡邊公彦, 齋藤諭, 橋本恵理, 齋藤利和, 相馬仁

アルコールと医学生物学 ( (株)響文社 ) 27 16 - 23 2007.09

アルコールが小胞体に及ぼす影響を明らかにする目的で、プロテオミクス技術を用いて、神経幹細胞にエタノールを処置した際の網羅的蛋白質発現変動の解析を試みるとともに、小胞体への特定分子の蓄積に着目した、小胞体機能変化の検討を試みた。ラット胎仔終脳から得た神経幹細胞を用いた。エタノールによって小胞体ストレス関連蛋白質を含んだ数種類のシャペロン蛋白質の発現が変動した。小胞体ストレス反応系エフェクターであるPERKがエタノール処置によって活性化し、エタノール処置により小胞体分画に蛋白質が蓄積した。エタノールによる神経幹細胞の神経細胞分化抑制作用に、小胞体機能の変化および転写抑制因子NRSFの結合活性変化の関与が考えられた。

Olanzapine potentiates neuronal survival and neural stem cell differentiation: regulation of endoplasmic reticulum stress response proteins

S. Kurosawa, E. Hashimoto, W. Ukai, S. Toki, S. Saito, T. Saito

JOURNAL OF NEURAL TRANSMISSION ( SPRINGER WIEN ) 114 ( 9 ) 1121 - 1128 2007.09 [Refereed]

Recent clinical neuroimaging studies have suggested that morphological brain changes occur and progress in the course of schizophrenia. Although the neurogenetic and neurotrophic effects of antipsychotics are considered to contribute to the prevention of reduction in brain volume, the cellular molecular mechanisms of action of antipsychotics have not yet been elucidated. We examined the effects of antipsychotics on the endoplasmic reticulum (ER) stress-induced damages of neurons and neural stem cells (NSCs) using cultured cells. In the neuronal cultures, the atypical antipsychotic olanzapine protected neurons from thapsigargin (1 mu M)-induced injury. It was observed that a low concentration of thapsigargin (10 nM) that did not affect the neuronal survival could reduce neuronal differentiation of cultured NSCs, suggesting a role of ER stress in the differentiation function of NSCs. Treatment with olanzapine increased the neuronal differentiation suppressed by the exposure to thapsigargin (10 nM). The thapsigargin-induced ER chaperones, GRP78, which indicate the ER stress condition of the cell, were decreased by the treatment with the atypical antipsychotics olanzapine and quetiapine but not by the typical antipsychotic haloperidol. These results indicate that the amelioration of ER-stress might be involved in the cellular mechanisms of atypical antipsychotics to produce neuroprotective and neurogenetic actions in neurons and NSCs, suggesting potential roles of these drugs for treatment of schizophrenia.

DOI

Evaluation of whole genome amplification methods using postmortem brain samples

Kazuya Iwamoto, Junko Ueda, Yoko Nakano, Miki Bundo, Wataru Ukai, Eri Hashimoto, Toshikazu Saito, Tadafumi Kato

JOURNAL OF NEUROSCIENCE METHODS ( ELSEVIER SCIENCE BV ) 165 ( 1 ) 104 - 110 2007.09 [Refereed]

The importance of examining genomic DNA derived from human brain has been highlighted by recent findings such as the possible link between DNA methylation and behavior or mental disorders, as well as the possible genomic differences between neurons from the same individual caused by transposons and aneuploidy. Consequently, obtaining a sufficient amount of genomic DNA derived from human brain is a critical issue for further research. Whole genome amplification (WGA) methods, by which genomic DNA is typically amplified on the order of 10(4)-10(6), will be a valuable tool for providing a sufficient amount of DNA for various molecular genetic studies. Here we evaluated three methods, including both PCR-based and non-PCR based WGA, as well as DNA extraction methods using frozen postmortem brain tissue. We found that WGA products from postmortem brains can be used in molecular genetic analysis, if a particular protocol for DNA extraction is used, and the most appropriate method for WGA depends on the state of the genomic DNA to be amplified. (c) 2007 Elsevier B.V. All rights reserved.

DOI PubMed

Analysis of possible cellular mechanism of ethanol-induced neural stem cell dysfunction

UKAI W, ISHII T, YOSHINAGA T, TATENO M, HASHIMOTO E, SAITO S, SAITO T

日本アルコール・薬物医学会雑誌 = Japanese journal of alcohol studies & drug dependence 42 ( 4 ) 230 - 231 2007.08

CiNii

Trichostatin A can block ethanol-induced neurogenesis disturbance by transcriptional regulation change

ISHII Takao, UKAI Wataru, YOSHINAGA Toshihiro, TATENO Masaru, Hashimoto Eri, 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 ) 42 ( 4 ) 420 - 421 2007.08

CiNii

アルコール・薬物依存の基礎研究の動向エタノールによる神経幹細胞機能異常の細胞内メカニズム解析

鵜飼渉, 石井貴男, 吉永敏弘, 館農勝, 橋本恵理, 齋藤諭, 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 ) 42 ( 4 ) 230 - 231 2007.08

Effects of psychotropic drugs on neurogenesis and cytokine signaling

HASHIMOTO Eri, UKAI Wataru, IMAI Tomoyuki, ISHII Takao, KUROSAWA Shigeki, YOSHINAGA Toshihiro, SAITO Satoshi, SAITO Toshikazu

脳と精神の医学 = Brain science and mental disorders 18 ( 2 ) 103 - 110 2007.06

CiNii J-GLOBAL

The neural network reconstruction as a new therapy for treatment-resistant neuropsychiatric disorders

鵜飼渉, 橋本恵理, 石井貴男, 吉永敏弘, 館農勝, 齋藤諭, 齋藤利和

札幌医学雑誌 ( 札幌医科大学医学部 ) 76 ( 1 ) 7 - 12 2007.06

Neural stem cells (NSCs) have recently been identified in mammalian brains, including human. The long-standing dogma of "no new neuron" was overturned by the discovery of NSCs in the adult brain. NSCs are primordial and uncommitted cells with two characteristic properties; self-renewal and multipotency. NSCs give rise to various types of cells in the central nervous system including neurons, astrocytes and oligodendrocytes. NSCs attract interests of a large number of researchers in various scientific fields because of their possibility of becoming innovative therapeutic strategy for neurodegenerative disorders previously considered untreatable. Recent clinical neuroimaging studies have suggested that morphological brain changes occur and progress in the course of depression, Alzheimer's disease and schizophrenia. The analysis of potentials of psychotropic drugs on NSC function may reveal the pathophysiological importance of neural network impairment and its repair. Furthermore, the studies using stem cells such as intravenous NSC transplantation can be a useful method to clarify the neural network reconstruction mechanism damaged in neuropsychiatric disorders.

DOI CiNii

アルコールによる神経幹細胞分化抑制脳神経回路網改築・維持への影響

橋本恵理

日本アルコール精神医学雑誌 ( 日本アルコール精神医学会 ) 14 ( 1 ) 11 - 17 2007.06

近年、胎児期のみならず成人においても神経新生の基となる神経幹細胞の存在が確認され、神経新生の異常がアルコールによる脳障害の病態基盤に関わっていることが推察されている。すなわち、アルコールによる成熟神経細胞障害のみならず、神経幹細胞の分化機能変化もまた、脳神経回路網の構築や維持に重大な影響を与えるものと考えられる。本稿では、アルコールが神経回路網に与える影響に関して、神経幹細胞の分化機能への抑制的作用を中心に概説し、加えて、アルコールによる障害のメカニズムを知ることで新たな治療法の可能性を探る試みを紹介する。(著者抄録)

【生体防御機構と精神疾患】向精神薬による神経新生増強とサイトカインシグナル伝達

橋本恵理, 鵜飼渉, 今井智之, 石井貴男, 黒澤茂樹, 吉永敏弘, 齋藤諭, 齋藤利和

脳と精神の医学 ( 日本生物学的精神医学会 ) 18 ( 2 ) 103 - 110 2007.06

J-GLOBAL

抗うつ薬の作用機序に関する新たな視点での考察

今井智之, 鵜飼渉, 石井貴男, 黒澤茂樹, 吉永敏弘, 小野貴文, 館農勝, 齋藤諭, 橋本恵理, 池田官司, 齋藤利和

分子精神医学 ( (株)先端医学社 ) 7 ( 2 ) 161 - 163 2007.04

J-GLOBAL

The analysis of repair and regeneration of neural network by antidepressants: In vitro and in vivo studies using neural stem cells

鵜飼渉, 今井智之, 石井貴男, 黒澤茂樹, 吉永敏弘, 小野貴文, 館農勝, 畠山佳久, 齋藤諭, 橋本恵理, 齋藤利和

精神薬療研究年報 ( (公財)先進医薬研究振興財団 ) ( 39 ) 209 - 218 2007.03

抗うつ薬投与による神経幹細胞内のシグナル伝達系変化及び転写因子調節機構について解析した。さらに、胎児性アルコール症候群のモデル動物に標識した神経幹細胞を移植する方法で、神経幹細胞の脳内動態の可視化を図るとともに、行動学的評価による神経回路修復機構についてin vivo解析を試みた。細胞に各種抗うつ薬、及び小胞体ストレスを処置した際の神経幹細胞の分化決定に重要な役割を担う転写抑制因子NRSF/RESTの活性変化について検討し、その細胞内調節機構について新たな知見が得られた。また、培養神経幹細胞を精神疾患モデルラットに移植し脳内での神経新生を可視化する方法で、神経回路網修復機序についてin vivo解析を試み、脳内での分布動態を示すとともに、神経幹細胞の経静脈的移植による精神疾患モデル動物の行動学的な改善効果を明らかにした。

J-GLOBAL

Neural stem cell transplantation in a model of fetal alcohol effects

T. Yoshinaga, E. Hashimoto, W. Ukai, S. Toki, S. Saito, T. Saito

JOURNAL OF NEURAL TRANSMISSION-SUPPLEMENT ( SPRINGER ) ( 72 ) 331 - 337 2007 [Refereed]

Neural stem cell (NSC) transplantation has been investigated and developed in areas such as brain injury, stroke and neurodegenerative diseases. Recently, emerging evidence suggest that many of clinical symptoms observed in psychiatric disease are likely related to neural network disruptions including neurogenesis dysfunction. In the present study, we transplanted NSCs into a model of fetal alcohol effects (FAE) for the purpose of investigating the possibility of regenerative therapy for FAE. We labeled NSCs with fluorescent dye and radioisotope which were transplanted into FAE rats by intravenous injection. The transplanted cells were detected in wide areas of brain and were greater in number in the brains of the FAE group compared to the control group. Furthermore NSC transplantation attenuated behavioral abnormalities in FAE animals. These results suggest NSC transplantation as a potential new therapy for human FAE.

アルコール曝露モデルを用いた精神疾患への神経幹細胞移植(Neural stem cell transplantation for psychiatric disease using alcohol exposure model)

Yoshinaga Toshihiro, Ukai Wataru, Ishii Takao, Imai Tomoyuki, Kurosawa Shigeki, Ono Takafumi, Saito Satoshi, Hashimoto Eri, Ikeda Hiroshi, Saito Toshikazu

日本神経精神薬理学雑誌 ( (一社)日本神経精神薬理学会 ) 26 ( 5-6 ) 258 - 258 2006.11

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Papers - HASHIMOTO Eri