2025/07/03 更新

写真a

マツイ ヒデアキ
松井 秀彰
MATSUI Hideaki
所属
脳研究所 生命科学リソース研究センター 教授
職名
教授
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外部リンク

学位

  • 博士(医学) ( 2010年3月   京都大学 )

研究キーワード

  • パーキンソン病

  • アフリカメダカ

  • 神経変性疾患

  • ゼブラフィッシュ

  • メダカ

  • ヒト剖検脳

  • 神経科学

  • 自閉症

  • 加齢関連疾患

  • 老化

  • 多系統萎縮症

  • 筋萎縮性側索硬化症

  • アルツハイマー病

研究分野

  • ライフサイエンス / 神経科学一般

  • ライフサイエンス / 神経内科学

  • ライフサイエンス / 栄養学、健康科学

  • ライフサイエンス / 分子生物学

経歴(researchmap)

  • 新潟大学   脳研究所附属生命科学リソース研究センター   センター長

    2024年3月 - 現在

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  • 新潟大学   脳研究所   副所長

    2024年2月 - 現在

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  • 新潟大学   脳研究所 脳病態解析分野   教授

    2020年4月 - 現在

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  • 新潟大学   研究推進機構   教授

    2020年4月

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    国名:日本国

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  • 新潟大学   超域学術院 脳病態解析分野 (脳研究所)   テニュアトラック准教授

    2016年1月 - 2020年3月

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  • 新潟大学   研究教授

    2016年 - 2020年3月

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  • 宮崎大学   医学部

    2013年1月 - 2016年1月

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  • TU Braunschweig   Department of CellPhysiology

    2011年1月 - 2012年12月

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  • 住友病院   神経内科   医員

    2004年6月 - 2006年3月

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  • 住友病院   総合診療科   医員

    2003年4月 - 2004年5月

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  • 住友病院   総合診療科   研修医

    2002年6月 - 2003年3月

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  • 京都大学病院   内科   研修医

    2001年5月 - 2002年5月

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経歴

  • 新潟大学   脳研究所 生命科学リソース研究センター   教授

    2020年4月 - 現在

  • 新潟大学   研究推進機構 超域学術院   准教授

    2016年1月 - 2020年3月

学歴

  • 京都大学   Graduate School of Medicine

    2006年4月 - 2010年3月

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  • 京都大学   Faculty of Medicine   Department of Medical Science

    1994年4月 - 2001年3月

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所属学協会

委員歴

  • 日本神経科学学会   評議員  

    2023年4月 - 現在   

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    団体区分:学協会

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  • 脳科学関連学会連合   庶務幹事  

    2023年1月 - 現在   

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    団体区分:学協会

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  • NBRP ゼブラフィッシュ   第5期(2022~2026年度)運営委員  

    2022年4月 - 現在   

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    団体区分:学協会

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  • 新潟生化学懇話会   世話人  

    2021年4月 - 現在   

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    団体区分:学協会

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  • 第63回日本神経学会学術大会   年次学術委員  

    2021年1月 - 2023年1月   

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  • 第43回日本神経科学大会   プログラム委員  

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  • 2020年度小型魚類研究会   実行委員  

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取得資格

  • 医師

 

論文

  • Exploring α-Syn's Functions Through Ablation Models: Physiological and Pathological Implications. 査読 国際誌

    Anjali Praveen, Godfried Dougnon, Hideaki Matsui

    Cellular and molecular neurobiology   45 ( 1 )   44 - 44   2025年5月

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

    A significant advancement in neurodegenerative research was the discovery that α-synuclein (α-Syn/SNCA) plays a part in the pathophysiology of Parkinson's disease (PD). Decades later, the protein's significant impacts on various brain disorders are still being extensively explored. In disease conditions, α-Syn misfolds and forms abnormal aggregates that accumulate in neurons, thus triggering various organellar dysfunctions and ultimately neurodegeneration. These misfolded forms are highly heterogeneous and vary significantly among different synucleinopathies, such as PD, Multiple System Atrophy, or Dementia with Lewy bodies. Though initially believed to be exclusively localized in the brain, numerous pieces of evidence suggest that α-Syn functions transcend the central nervous system, with roles in peripheral functions, such as modulation of immune responses, hematopoiesis, and gastrointestinal regulation. Here, we aim to provide a detailed compilation of cellular functions and pathological phenotypes that are altered upon attenuation of α-Syn function in vitro and in vivo and explore the effects of SNCA gene silencing in healthy and disease states using cellular and animal models.

    DOI: 10.1007/s10571-025-01560-2

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  • Phosphorylation of optineurin by TBK1 drives fragmentation of Golgi apparatus. 査読 国際誌

    Md Nazmul Islam, Tomoyuki Yamanaka, Hideaki Matsui

    Biochemical and biophysical research communications   752   151447 - 151447   2025年2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)  

    Optineurin (OPTN) is a multifunctional adaptor protein involved in various cellular processes. One critical function is maintaining the Golgi complex, as OPTN depletion or its disease-associated mutations leads to Golgi fragmentation. On the other hand, OPTN is known to be phosphorylated by TBK1 to regulate specific cellular processes; however, its role in Golgi regulation remains unclear. Here, we show that expression of a phosphomimetic OPTN mutant, S177E, but not its phospho-deficient mutant, S177A, in HeLa cells effectively results in fragmentation of the Golgi apparatus. Although the effect of S177E appears similar to that of disease-associated OPTN mutations such as E50K, experiments using OPTN double mutants suggest that S177E induces Golgi fragmentation possibly through an E50K-independent pathway. Furthermore, we found that Ser177 phosphorylation in OPTN is enhanced by TBK1, and co-expression of TBK1 with wild-type OPTN induces Golgi fragmentation. Notably, Ser177 phosphorylation leads to the formation of cytoplasmic OPTN puncta, correlating with Golgi fragmentation. Taken together, our data suggest that OPTN phosphorylation by TBK1 induces ectopic OPTN accumulation, leading to Golgi disassembly, possibly via a novel pathway distinct from those associated with disease-related OPTN mutations.

    DOI: 10.1016/j.bbrc.2025.151447

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  • Three decades of neuroscience research using animal models of ADHD and ASD: a bibliometric analysis. 査読 国際誌

    Godfried Dougnon, Hideaki Matsui

    Frontiers in psychiatry   16   1528205 - 1528205   2025年

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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)  

    INTRODUCTION: Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorders (ASD) are two increasingly prevalent neurodevelopmental disorders (NDDs), often accompanied by significant daily-life challenges. Animal models play a crucial role in studying these conditions, and recent advances have highlighted the potential of animal models such as mice, rat, zebrafish, Drosophila or Caenorhabditis elegans for investigating NDDs. However, despite growing interest, a complete understanding of these disorders has yet to be achieved. We believe that to properly address these NDDs, it is important to analyze the heterogeneity of ADHD and ASD research. METHODS: This study comprehensively analyzes ADHD and ASD-related scientific publications from January 1990 to December 2023 using data from the Web of Science (WoS), exploring trends in global research output, impact factors, citation metrics, the predominant use of animal models, the contribution of major countries and funding information. RESULTS: Out of the 10,844 papers from WoS, we curated 5,883 papers and identify mice and rat as the primarily used animal models, and a progressive use of zebrafish, Drosophila and C. elegans since the early 2000s. The countries conducting research on ADHD and ASD were principally the United States (3,059 articles), followed by China (487 articles), the United Kingdom (459 articles), Japan (440 articles), Germany (413 articles). We further show that impact factors and journal citations were relatively similar among the major publishing countries. Interestingly, key research funders were the National Institute of Health (NIH), the National Institute of Mental Health (NIMH), and the Japanese Ministry of Education Culture Sports Science and Technology (MEXT), making important contributions to their respective countries' publications. Of note, Africa and Oceania have a lower volume of publication; however, our network analysis indicates a recent peak in research interest and ADHD/ASD awareness in some countries like Ghana or Portugal. CONCLUSION: The findings highlight significant advancements and collaborative efforts in ADHD and ASD research over the last three decades, underscoring the importance of international cooperation in addressing these complex neurodevelopmental disorders.

    DOI: 10.3389/fpsyt.2025.1528205

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  • Homozygous slc25a20 Zebrafish Mutant Reveals Insights into Carnitine-Acylcarnitine Translocase Deficiency Pathogenesis. 査読

    Ryuichi Hishida, Kohei Ishiguro, Tomoyuki Yamanaka, Shinya Toyokuni, Hideaki Matsui

    Molecular Genetics and Metabolism Reports   41   101165 - 101165   2024年12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)  

    DOI: 10.1016/j.ymgmr.2024.101165

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  • Single housing of juveniles accelerates early-stage growth but extends adult lifespan in African turquoise killifish. 査読 国際誌

    Chika Takahashi, Emiko Okabe, Masanori Nono, Saya Kishimoto, Hideaki Matsui, Tohru Ishitani, Takuya Yamamoto, Masaharu Uno, Eisuke Nishida

    Aging   16   2024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)  

    Within the same species, individuals exhibiting faster growth tend to have shorter lifespans, even if their fast growth arises from early-life pharmacological interventions. However, in vertebrates, the impact of the early-life environment on the growth rate and lifespan has not been fully elucidated. In this study, by utilizing the short-lived African turquoise killifish, which is suitable for a comprehensive life-stage analysis in a brief timeframe, we explored the effects of housing density during the juvenile stage on holistic life traits. As a result, we found that lower housing densities resulted in faster growth, but led to longer adult lifespan, which was contrary to the common notion. Furthermore, the single-housed adult fish displayed a longer egg-laying period than did their group-housed counterparts. Our transcriptome analysis also demonstrated that, in terms of internal transcriptional programs, the life stage progression and aging process of single-housed fish were slower than those of group-housed fish. Collectively, our results suggest that sharing housing with others in early life might influence whole-life attributes, potentially leading to specific life history traits beyond the typical relationship between the growth rate and lifespan.

    DOI: 10.18632/aging.206111

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  • Current trends in basic research on Parkinson's disease: from mitochondria, lysosome to α-synuclein. 招待 査読 国際誌

    Hideaki Matsui, Ryosuke Takahashi

    Journal of neural transmission (Vienna, Austria : 1996)   2024年4月

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

    Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive degeneration of dopaminergic neurons in the substantia nigra and other brain regions. A key pathological feature of PD is the abnormal accumulation of α-synuclein protein within affected neurons, manifesting as Lewy bodies and Lewy neurites. Despite extensive research efforts spanning several decades, the underlying mechanisms of PD and disease-modifying therapies remain elusive. This review provides an overview of current trends in basic research on PD. Initially, it discusses the involvement of mitochondrial dysfunction in the pathogenesis of PD, followed by insights into the role of lysosomal dysfunction and disruptions in the vesicular transport system. Additionally, it delves into the pathological and physiological roles of α-synuclein, a crucial protein associated with PD pathophysiology. Overall, the purpose of this review is to comprehend the current state of elucidating the intricate mechanisms underlying PD and to outline future directions in understanding this disease.

    DOI: 10.1007/s00702-024-02774-2

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  • Extracellular disposal of nuclear waste by APP: a protective mechanism impaired in Alzheimer’s disease

    Godfried Dougnon, Takayoshi Otsuka, Yuka Nakamura, Akiko Sakai, Tomoyuki Yamanaka, Noriko Matsui, Asa Nakahara, Ai Ito, Atsushi Hatano, Masaki Matsumoto, Hironaka Igarashi, Akiyoshi Kakita, Masaki Ueno, Hideaki Matsui

    2024年2月

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    出版者・発行元:Cold Spring Harbor Laboratory  

    Abstract

    Although the amyloid beta (Aβ) hypothesis<sup>1</sup>has long been central to Alzheimer’s disease (AD) research, effective therapeutic strategies remain elusive<sup>2,3</sup>. Here we re-evaluate the functions of amyloid precursor protein (APP) and reveal its critical function in protecting against nuclear impairment-induced cell death and inflammation<sup>4,5</sup>. Overexpression of APP mitigated etoposide or lamin A knockdown-induced nuclear damage, while APP removal or mutations exacerbated these effects. Interestingly, neurons differentiated from induced pluripotent stem cells (iPSCs) exhibited similar patterns, and notably, familial AD-associated mutant APP failed to confer protection against nuclear impairment. We identify APP’s interaction with a cytoplasmic structure of nuclear origin, termed “nuclear waste”, and propose its role in extracellular waste disposal. Intriguingly, cells lacking APP showed impaired nuclear waste clearance, leading to abnormal cytoplasmic accumulation of the nuclear waste. Similarly, neuron-specific APP overexpression using adeno-associated virus (AAV) in mice reduced neuronal death and inflammation caused by nuclear damage. Conversely, shRNA-mediated APP exacerbated these effects, and mutant APP associated with familial AD lacked protective effects. Moreover, postmortem analysis of AD brains revealed accumulation of abnormal nuclear waste in the neurocytoplasm, irregular nuclear morphology, and reduced APP levels per neuron. Our data underscore APP’s crucial role in disposing of nuclear waste, maintaining cellular homeostasis, and suggest its dysregulation as a potential contributor to AD pathogenesis. Restoring APP waste clearance in AD could be a promising target for disease-modifying therapies.

    DOI: 10.1101/2024.02.10.579739

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  • The Transcription factor NF-YA is Crucial for Neural Progenitor Maintenance during Brain Development. 査読 国際誌

    Tomoyuki Yamanaka, Masaru Kurosawa, Aya Yoshida, Tomomi Shimogori, Akiko Hiyama, Sankar N Maity, Nobutaka Hattori, Hideaki Matsui, Nobuyuki Nukina

    The Journal of biological chemistry   105629 - 105629   2024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)  

    In contrast to stage-specific transcription factors, the role of ubiquitous transcription factors in neuronal development remains a matter of scrutiny. Here, we demonstrated that a ubiquitous factor NF-Y is essential for neural progenitor maintenance during brain morphogenesis. Deletion of the NF-YA subunit in neural progenitors by using nestin-cre transgene in mice resulted in significant abnormalities in brain morphology, including a thinner cerebral cortex and loss of striatum during embryogenesis. Detailed analyses revealed a progressive decline in multiple neural progenitors in the cerebral cortex and ganglionic eminences, accompanied by induced apoptotic cell death and reduced cell proliferation. In neural progenitors, the NF-YA short isoform lacking exon 3 is dominant and co-expressed with cell cycle genes. ChIP-seq analysis from the cortex during early corticogenesis revealed preferential binding of NF-Y to the cell cycle genes, some of which were confirmed to be downregulated following NF-YA deletion. Notably, the NF-YA short isoform disappears and is replaced by its long isoform during neuronal differentiation. Forced expression of the NF-YA long isoform in neural progenitors resulted in a significant decline in neuronal count, possibly due to the suppression of cell proliferation. Collectively, we elucidated a critical role of the NF-YA short isoform in maintaining neural progenitors, possibly by regulating cell proliferation and apoptosis. Moreover, we identified an isoform switch in NF-YA within the neuronal lineage in vivo, which may explain the stage-specific role of NF-Y during neuronal development.

    DOI: 10.1016/j.jbc.2024.105629

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  • GPATCH4 contributes to nucleolus morphology and its dysfunction impairs cell viability. 査読 国際誌

    Kazuki Kodera, Ryuichi Hishida, Akiko Sakai, Hiromi Nyuzuki, Noriko Matsui, Tomoyuki Yamanaka, Akihiko Saitoh, Hideaki Matsui

    Biochemical and biophysical research communications   693   149384 - 149384   2023年12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)  

    The nucleolus serves a multifaceted role encompassing not only rRNA transcription and ribosome synthesis, but also the intricate orchestration of cell cycle regulation and the modulation of cellular senescence. G-patch domain containing 4 (GPATCH4) stands as one among the nucleolar proteins; however, its functional significances remain still unclear. In order to elucidate the functions of GPATCH4, we examined the effects of its dysfunction on cellular proliferation, alterations in nucleolar architecture, apoptotic events, and cellular senescence. Through experimentation conducted on cultured neuroblastoma SH-SY5Y cells, the reduction of GPATCH4 caused inhibition of cellular proliferation, concurrently fostering escalated apoptotic susceptibilities upon exposure to high-dose etoposide. In the realm of nucleolar morphology comparisons, a discernible decline was noted in the count of nucleoli per nucleus, concomitant with a significant expansion in the area occupied by individual nucleoli. Upon induction of senescence prompted by low-dose etoposide, GPATCH4 knockdown resulted in decreased cell viability and increased expression of senescence-associated markers, namely senescence-associated β-galactosidase (SA-β-GAL) and p16. Furthermore, GPATCH4 dysfunction elicited alterations in the gene expression profile of the ribosomal system. In sum, our findings showed that GPATCH4 is a pivotal nucleolar protein that regulates nucleolar morphology and is correlated with cell viability.

    DOI: 10.1016/j.bbrc.2023.149384

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  • Modeling familial and sporadic Parkinson's disease in small fishes. 招待 査読

    Tomoyuki Yamanaka, Hideaki Matsui

    Development, growth & differentiation   2023年11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)  

    The establishment of animal models for Parkinson's disease (PD) has been challenging. Nevertheless, once established, they will serve as valuable tools for elucidating the causes and pathogenesis of PD, as well as for developing new strategies for its treatment. Following the recent discovery of a series of PD causative genes in familial cases, teleost fishes, including zebrafish and medaka, have often been used to establish genetic PD models because of their ease of breeding and gene manipulation, as well as the high conservation of gene orthologs. Some of the fish lines can recapitulate PD phenotypes, which are often more pronounced than those in rodent genetic models. In addition, a new experimental teleost fish, turquoise killifish, can be used as a sporadic PD model, because it spontaneously manifests age-dependent PD phenotypes. Several PD fish models have already made significant contributions to the discovery of novel PD pathological features, such as cytosolic leakage of mitochondrial DNA and pathogenic phosphorylation in α-synuclein. Therefore, utilizing various PD fish models with distinct degenerative phenotypes will be an effective strategy for identifying emerging facets of PD pathogenesis and therapeutic modalities.

    DOI: 10.1111/dgd.12904

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  • Phosphorylation of α-synuclein at T64 results in distinct oligomers and exerts toxicity in models of Parkinson's disease. 査読 国際誌

    Hideaki Matsui, Shinji Ito, Hideki Matsui, Junko Ito, Ramil Gabdulkhaev, Mika Hirose, Tomoyuki Yamanaka, Akihide Koyama, Taisuke Kato, Maiko Tanaka, Norihito Uemura, Noriko Matsui, Sachiko Hirokawa, Maki Yoshihama, Aki Shimozawa, Shin-Ichiro Kubo, Kenji Iwasaki, Masato Hasegawa, Ryosuke Takahashi, Keisuke Hirai, Akiyoshi Kakita, Osamu Onodera

    Proceedings of the National Academy of Sciences of the United States of America   120 ( 23 )   e2214652120   2023年6月

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

    α-Synuclein accumulates in Lewy bodies, and this accumulation is a pathological hallmark of Parkinson's disease (PD). Previous studies have indicated a causal role of α-synuclein in the pathogenesis of PD. However, the molecular and cellular mechanisms of α-synuclein toxicity remain elusive. Here, we describe a novel phosphorylation site of α-synuclein at T64 and the detailed characteristics of this post-translational modification. T64 phosphorylation was enhanced in both PD models and human PD brains. T64D phosphomimetic mutation led to distinct oligomer formation, and the structure of the oligomer was similar to that of α-synuclein oligomer with A53T mutation. Such phosphomimetic mutation induced mitochondrial dysfunction, lysosomal disorder, and cell death in cells and neurodegeneration in vivo, indicating a pathogenic role of α-synuclein phosphorylation at T64 in PD.

    DOI: 10.1073/pnas.2214652120

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  • Fish Models for Exploring Mitochondrial Dysfunction Affecting Neurodegenerative Disorders 査読 国際誌

    Takayoshi Otsuka, Hideaki Matsui

    International Journal of Molecular Sciences   24 ( 8 )   7079 - 7079   2023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   掲載種別:研究論文(学術雑誌)   出版者・発行元:MDPI AG  

    Neurodegenerative disorders are characterized by the progressive loss of neuronal structure or function, resulting in memory loss and movement disorders. Although the detailed pathogenic mechanism has not been elucidated, it is thought to be related to the loss of mitochondrial function in the process of aging. Animal models that mimic the pathology of a disease are essential for understanding human diseases. In recent years, small fish have become ideal vertebrate models for human disease due to their high genetic and histological homology to humans, ease of in vivo imaging, and ease of genetic manipulation. In this review, we first outline the impact of mitochondrial dysfunction on the progression of neurodegenerative diseases. Then, we highlight the advantages of small fish as model organisms, and present examples of previous studies regarding mitochondria-related neuronal disorders. Lastly, we discuss the applicability of the turquoise killifish, a unique model for aging research, as a model for neurodegenerative diseases. Small fish models are expected to advance our understanding of the mitochondrial function in vivo, the pathogenesis of neurodegenerative diseases, and be important tools for developing therapies to treat diseases.

    DOI: 10.3390/ijms24087079

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  • Functional regionalization of the differentiating cerebellar Purkinje cell population occurs in an activity-dependent manner. 査読 国際誌

    Alessandro Dorigo, Komali Valishetti, Florian Hetsch, Hideaki Matsui, Jochen C Meier, Kazuhiko Namikawa, Reinhard W Köster

    Frontiers in molecular neuroscience   16   1166900 - 1166900   2023年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    INTRODUCTION: The cerebellum is organized into functional regions each dedicated to process different motor or sensory inputs for controlling different locomotor behaviors. This functional regionalization is prominent in the evolutionary conserved single-cell layered Purkinje cell (PC) population. Fragmented gene expression domains suggest a genetic organization of PC layer regionalization during cerebellum development. However, the establishment of such functionally specific domains during PC differentiation remained elusive. METHODS AND RESULTS: We show the progressive emergence of functional regionalization of PCs from broad responses to spatially restricted regions in zebrafish by means of in vivo Ca2+-imaging during stereotypic locomotive behavior. Moreover, we reveal that formation of new dendritic spines during cerebellar development using in vivo imaging parallels the time course of functional domain development. Pharmacological as well as cell-type specific optogenetic inhibition of PC neuronal activity results in reduced PC dendritic spine density and an altered stagnant pattern of functional domain formation in the PC layer. DISCUSSION: Hence, our study suggests that functional regionalization of the PC layer is driven by physiological activity of maturing PCs themselves.

    DOI: 10.3389/fnmol.2023.1166900

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  • Rapid reverse genetics systems for Nothobranchius furzeri, a suitable model organism to study vertebrate aging 査読 国際誌

    Masayuki Oginuma, Moana Nishida, Tomomi Ohmura-Adachi, Kota Abe, Shohei Ogamino, Chihiro Mogi, Hideaki Matsui, Tohru Ishitani

    Scientific Reports   12 ( 1 )   11628 - 11628   2022年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Science and Business Media LLC  

    Abstract

    The African turquoise killifish Nothobranchius furzeri (N. furzeri) is a useful model organism for studying aging, age-related diseases, and embryonic diapause. CRISPR/Cas9-mediated gene knockout and Tol2 transposon-mediated transgenesis in N. furzeri have been reported previously. However, these methods take time to generate knockout and transgenic fish. In addition, knock-in technology that inserts large DNA fragments as fluorescent reporter constructs into the target gene in N. furzeri has not yet been established. Here, we show that triple-target CRISPR-mediated single gene disruption efficiently produces whole-body biallelic knockout and enables the examination of gene function in the F0 generation. In addition, we developed a method for creating the knock-in reporter N. furzeri without crossing by optimizing the CRISPR/Cas9 system. These methods drastically reduce the duration of experiments, and we think that these advances will accelerate aging and developmental studies using N. furzeri.

    DOI: 10.1038/s41598-022-15972-3

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    その他リンク: https://www.nature.com/articles/s41598-022-15972-3

  • Cellular response against cytosolic leakage of mitochondrial DNA 査読 国際誌

    Sakai Akiko, Matsui Hideaki

    Neural Regeneration Research   17 ( 12 )   2682 - 2684   2022年12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)  

    DOI: 10.4103/1673-5374.335816

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  • Glutamatergic pathways in the brains of turtles: A comparative perspective among reptiles, birds, and mammals 査読 国際誌

    Mohammad Tufazzal Hussan, Akiko Sakai, Hideaki Matsui

    Frontiers in Neuroanatomy   16   937504 - 937504   2022年8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:Frontiers Media SA  

    Glutamate acts as the main excitatory neurotransmitter in the brain and plays a vital role in physiological and pathological neuronal functions. In mammals, glutamate can cause detrimental excitotoxic effects under anoxic conditions. In contrast, Trachemys scripta, a freshwater turtle, is one of the most anoxia-tolerant animals, being able to survive up to months without oxygen. Therefore, turtles have been investigated to assess the molecular mechanisms of neuroprotective strategies used by them in anoxic conditions, such as maintaining low levels of glutamate, increasing adenosine and GABA, upregulating heat shock proteins, and downregulating K<sub>ATP</sub> channels. These mechanisms of anoxia tolerance of the turtle brain may be applied to finding therapeutics for human glutamatergic neurological disorders such as brain injury or cerebral stroke due to ischemia. Despite the importance of glutamate as a neurotransmitter and of the turtle as an ideal research model, the glutamatergic circuits in the turtle brain remain less described whereas they have been well studied in mammalian and avian brains. In reptiles, particularly in the turtle brain, glutamatergic neurons have been identified by examining the expression of vesicular glutamate transporters (VGLUTs). In certain areas of the brain, some ionotropic glutamate receptors (GluRs) have been immunohistochemically studied, implying that there are glutamatergic target areas. Based on the expression patterns of these glutamate-related molecules and fiber connection data of the turtle brain that is available in the literature, many candidate glutamatergic circuits could be clarified, such as the olfactory circuit, hippocampal–septal pathway, corticostriatal pathway, visual pathway, auditory pathway, and granule cell–Purkinje cell pathway. This review summarizes the probable glutamatergic pathways and the distribution of glutamatergic neurons in the pallium of the turtle brain and compares them with those of avian and mammalian brains. The integrated knowledge of glutamatergic pathways serves as the fundamental basis for further functional studies in the turtle brain, which would provide insights on physiological and pathological mechanisms of glutamate regulation as well as neural circuits in different species.

    DOI: 10.3389/fnana.2022.937504

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  • The Utility of Small Fishes for the Genetic Study of Human Age-Related Disorders 査読 国際誌

    Eisuke Dohi, Hideaki Matsui

    Frontiers in Genetics   13   928597 - 928597   2022年7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:Frontiers Media SA  

    Animal models have been used to model human diseases, and among them, small fishes have been highlighted for their usefulness in various ways, such as the low cost of maintenance, ease of genetic modification, small size for easy handling, and strength in imaging studies due to their relative transparency. Recently, the use of turquoise killifish, Nothobranchius furzeri, which is known to exhibit various aging phenotypes in a short period, has attracted attention in research on aging and age-related diseases. However, when using animal models, it is important to keep their genetic background and interspecies differences in mind for translating them into human diseases. In this article, we obtained the gene symbols of protein-coding genes of turquoise killifish, medaka, zebrafish, and humans from NCBI datasets and extracted common shared genes among four species to explore the potential of interspecies translational research and to apply small fish models for human age-related disorders. Common shared protein-coding genes were analyzed with the Reactome Pathway Database to determine the coverage of these genes in each pathway in humans. We applied common shared genes to the Orphanet database to establish a list of human diseases that contain common shared genes among the four species. As examples, the senescence-related pathways and some pathways of human age-related diseases, such as Alzheimer’s disease, Parkinson’s disease, frontotemporal dementia, nonalcoholic fatty liver disease, progeria, hepatocellular carcinoma, and renal cell carcinoma, were extracted from the curated pathway and disease list to discuss the further utility of fish models for human age-related disorders.

    DOI: 10.3389/fgene.2022.928597

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  • Modelling Autism Spectrum Disorder (ASD) and Attention-Deficit/Hyperactivity Disorder (ADHD) Using Mice and Zebrafish 査読 国際誌

    Godfried Dougnon, Hideaki Matsui

    International Journal of Molecular Sciences   23 ( 14 )   7550 - 7550   2022年7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:MDPI AG  

    Autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD) are two debilitating neurodevelopmental disorders. The former is associated with social impairments whereas the latter is associated with inattentiveness, hyperactivity, and impulsivity. There is recent evidence that both disorders are somehow related and that genes may play a large role in these disorders. Despite mounting human and animal research, the neurological pathways underlying ASD and ADHD are still not well understood. Scientists investigate neurodevelopmental disorders by using animal models that have high similarities in genetics and behaviours with humans. Mice have been utilized in neuroscience research as an excellent animal model for a long time; however, the zebrafish has attracted much attention recently, with an increasingly large number of studies using this model. In this review, we first discuss ASD and ADHD aetiology from a general point of view to their characteristics and treatments. We also compare mice and zebrafish for their similarities and discuss their advantages and limitations in neuroscience. Finally, we summarize the most recent and existing research on zebrafish and mouse models of ASD and ADHD. We believe that this review will serve as a unique document providing interesting information to date about these models, thus facilitating research on ASD and ADHD.

    DOI: 10.3390/ijms23147550

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  • Loss of GBA in zebrafish leads to dopaminergic neurodegeneration, but overexpression of α-synuclein does not further worsen degeneration. 査読 国際誌

    Kazuki Kodera, Noriko Matsui, Akihiko Saitoh, Hideaki Matsui

    Neuroreport   33 ( 7 )   320 - 325   2022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)  

    OBJECTIVES: Parkinson's disease is a neurodegenerative disorder that causes motor and nonmotor symptoms due to the loss of dopaminergic nerves and is characterized by the presence of Lewy bodies, which are mainly composed of α-synuclein. Glucosylceramidase beta (GBA), which is a causative gene of autosomal recessive Gaucher disease, is also known to be a risk gene for Parkinson's disease. In this study, we tried to detect synergistic effects of α-synuclein accumulation and gba depletion on dopaminergic neurodegeneration in zebrafish. METHODS: We generated a transgenic line of zebrafish overexpressing the A53T α-synuclein and gba mutant fish, and analyzed pathologies of α-synuclein aggregation and neurodegeneration. RESULTS: Zebrafish overexpressing the A53T α-synuclein did not exhibit α-synuclein aggregate formation. After the loss of gba function in this mutant α-synuclein transgenic line, we observed the marked presence of α-synuclein aggregates. Loss of gba function in zebrafish resulted in dopaminergic and noradrenergic neurodegeneration but this level of neurodegeneration was not exacerbated by overexpression of mutant α-synuclein. CONCLUSIONS: These results indicate that loss of gba function was sufficient to generate a neurodegenerative phenotype in zebrafish regardless of the expression of α-synuclein.

    DOI: 10.1097/WNR.0000000000001788

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  • Evaluation of Ectopic Mitochondrial DNA in HeLa Cells 査読

    Mohammad T. Hussan, Noriko Matsui, Hideaki Matsui

    Current Issues in Molecular Biology   44 ( 3 )   1215 - 1223   2022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)  

    DOI: 10.3390/cimb44030080

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  • Zebrafish, Medaka and Turquoise Killifish for Understanding Human Neurodegenerative/Neurodevelopmental Disorders. 査読 国際誌

    Kazuki Kodera, Hideaki Matsui

    International journal of molecular sciences   23 ( 3 )   2022年1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)  

    In recent years, small fishes such as zebrafish and medaka have been widely recognized as model animals. They have high homology in genetics and tissue structure with humans and unique features that mammalian model animals do not have, such as transparency of embryos and larvae, a small body size and ease of experiments, including genetic manipulation. Zebrafish and medaka have been used extensively in the field of neurology, especially to unveil the mechanisms of neurodegenerative diseases such as Parkinson's and Alzheimer's disease, and recently, these fishes have also been utilized to understand neurodevelopmental disorders such as autism spectrum disorder. The turquoise killifish has emerged as a new and unique model animal, especially for ageing research due to its unique life cycle, and this fish also seems to be useful for age-related neurological diseases. These small fishes are excellent animal models for the analysis of human neurological disorders and are expected to play increasing roles in this field. Here, we introduce various applications of these model fishes to improve our understanding of human neurological disorders.

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  • Cytosolic dsDNA of mitochondrial origin induces cytotoxicity and neurodegeneration in cellular and zebrafish models of Parkinson’s disease 査読 国際誌

    Hideaki Matsui, Junko Ito, Noriko Matsui, Tamayo Uechi, Osamu Onodera, Akiyoshi Kakita

    Nature Communications   12 ( 1 )   3101 - 3101   2021年

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    担当区分:筆頭著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Science and Business Media LLC  

    <title>Abstract</title>Mitochondrial dysfunction and lysosomal dysfunction have been implicated in Parkinson’s disease (PD), but the links between these dysfunctions in PD pathogenesis are still largely unknown. Here we report that cytosolic dsDNA of mitochondrial origin escaping from lysosomal degradation was shown to induce cytotoxicity in cultured cells and PD phenotypes in vivo. The depletion of PINK1, GBA and/or ATP13A2 causes increases in cytosolic dsDNA of mitochondrial origin and induces type I interferon (IFN) responses and cell death in cultured cell lines. These phenotypes are rescued by the overexpression of DNase II, a lysosomal DNase that degrades discarded mitochondrial DNA, or the depletion of IFI16, which acts as a sensor for cytosolic dsDNA of mitochondrial origin. Reducing the abundance of cytosolic dsDNA by overexpressing human DNase II ameliorates movement disorders and dopaminergic cell loss in gba mutant PD model zebrafish. Furthermore, IFI16 and cytosolic dsDNA puncta of mitochondrial origin accumulate in the brain of patients with PD. These results support a common causative role for the cytosolic leakage of mitochondrial DNA in PD pathogenesis.

    DOI: 10.1038/s41467-021-23452-x

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    その他リンク: http://www.nature.com/articles/s41467-021-23452-x

  • Esophageal High-Resolution Manometry for Diagnosing the Severity of the Chronic Intestinal Pseudo-Obstruction: A Case Series. 査読 国際誌

    Hiroki Sato, Kenya Kamimura, Hideaki Matsui, Takashi Owaki, Shinichi Morita, Yuto Tanaka, Natsuki Ishikawa, Yoshifumi Shimada, Junji Yokoyama, Toshifumi Wakai, Shuji Terai

    Digestive diseases and sciences   66 ( 11 )   3960 - 3967   2020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)  

    BACKGROUND: Chronic intestinal pseudo-obstruction (CIPO) is a severe and refractory intestinal motility disorder. However, due to its rarity and difficult histological investigation, its pathophysiology has not been characterized. AIM: Therefore, in this study, we aimed to determine the role of esophageal high-resolution manometry (HRM) in CIPO and the histological and clinical characteristics of the disease. METHODS: Patients with CIPO were analyzed for clinical characteristics; histological findings; and clinical courses after therapeutic intervention. In addition, HRM was performed to determine the esophageal involvement. RESULTS: Eleven patients were diagnosed with CIPO, and five required the long period of parenteral nutrition showing impaired esophageal motility including achalasia and absent contractility diagnosed with HRM. The four of these five cases showed acute onset of the CIPO following the triggering events of pregnancy, appendicitis, and surgery. In contrast, other six patients with normal or Jackhammer esophagus on HRM had moderate severity of CIPO with gradual onset. The histological analyses revealed that the loss of the intestinal neural ganglion cells and layers by inflammation, destruction, and atrophy are related to the severity of the clinical course of the disease and esophageal HRM findings of achalasia and absent contractility. CONCLUSIONS: HRM may be useful to diagnose the severity of the clinical course and to determine the therapeutic options for CIPO.

    DOI: 10.1007/s10620-020-06701-9

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  • Degeneration of dopaminergic neurons and impaired intracellular trafficking in Atp13a2 deficient zebrafish 査読 国際誌

    Hiromi Nyuzuki, Shinji Ito, Keisuke Nagasaki, Yohei Nitta, Noriko Matsui, Akihiko Saitoh, Hideaki Matsui

    IBRO Reports   9   1 - 8   2020年6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:Elsevier BV  

    ATP13A2 is the autosomal recessive causative gene for juvenile-onset Parkinson's disease (PARK9, Parkinson's disease 9), also known as Kufor-Rakeb syndrome. The disease is characterized by levodopa-responsive Parkinsonism, supranuclear gaze palsy, spasticity, and dementia. Previously, we have reported that Atp13a2 deficient medaka fish showed dopaminergic neurodegeneration and lysosomal dysfunction, indicating that lysosome-autophagy impairment might be one of the key pathogeneses of Parkinson's disease. Here, we established Atp13a2 deficient zebrafish using CRISPR/Cas9 gene editing. We found that the number of TH + neurons in the posterior tuberculum and the locus coeruleus significantly reduced (dopaminergic neurons, 64 % at 4 months and 37 % at 12 months, p < 0.001 and p < 0.05, respectively; norepinephrine neurons, 52 % at 4 months and 40 % at 12 months, p < 0.001 and p < 0.05, respectively) in Atp13a2 deficient zebrafish, proving the degeneration of dopaminergic neurons. In addition, we found the reduction (60 %, p < 0.05) of cathepsin D protein expression in Atp13a2 deficient zebrafish using immunoblot. Transmission electron microscopy analysis using middle diencephalon samples from Atp13a2 deficient zebrafish showed lysosome-like bodies with vesicle accumulation and fingerprint-like structures, suggesting lysosomal dysfunction. Furthermore, a significant reduction (p < 0.001) in protein expression annotated with vesicle fusion with Golgi apparatus in Atp13a2 deficient zebrafish by liquid-chromatography tandem mass spectrometry suggested intracellular trafficking impairment. Therefore, we concluded that Atp13a2 deficient zebrafish exhibited degeneration of dopaminergic neurons, lysosomal dysfunction and the possibility of intracellular trafficking impairment, which would be the key pathogenic mechanism underlying Parkinson's disease.

    DOI: 10.1016/j.ibror.2020.05.002

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  • Shrinkage of the myenteric neurons of the small intestine in patients with multiple system atrophy. 査読 国際誌

    Tetsutaro Ozawa, Hiroshi Shimizu, Hideaki Matsui, Osamu Onodera, Akiyoshi Kakita

    Autonomic neuroscience : basic & clinical   221   102583 - 102583   2019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)  

    This study aimed to determine whether enteric neurons are involved in multiple system atrophy (MSA). Four-μm-thick slices of small intestine were prepared from 10%-formalin-fixed and paraffin-embedded materials obtained from autopsied cases. Enteric neurons were stained using an anti-peripherin antibody. Immunostaining of phosphorylated α-synuclein was also performed. Areas of the cytoplasm and nucleus that showed nucleoli were measured using computer software. Both areas of myenteric neurons were significantly smaller in MSA cases (n = 3) than in control subjects (n = 3) (P < 0.0001); however, no deposits of phosphorylated α-synuclein were observed. These findings suggest that myenteric neurons in MSA are affected independent of α-synuclein accumulation.

    DOI: 10.1016/j.autneu.2019.102583

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  • Age- and α-Synuclein-Dependent Degeneration of Dopamine and Noradrenaline Neurons in the Annual Killifish Nothobranchius furzeri. 査読 国際誌

    Matsui H, Kenmochi N, Namikawa K

    Cell reports   26 ( 7 )   1727 - 1733   2019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  

    DOI: 10.1016/j.celrep.2019.01.015

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  • Parkinson's disease pathogenesis from the viewpoint of small fish models. 査読 国際誌

    Hideaki Matsui, Ryosuke Takahashi

    Journal of neural transmission (Vienna, Austria : 1996)   125 ( 1 )   25 - 33   2018年1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)  

    Parkinson's disease is a neurodegenerative disorder that involves movement discloses, degeneration of dopaminergic neurons, and presence of cytoplasmic inclusion bodies. Various animal models have been developed and small fish including zebrafish and medaka fish have recently been employed as a new model for Parkinson disease. In this review, we summarize fish models of Parkinson's disease mainly using our own findings and explain two major hypotheses of PD: lysosome dysfunction theory and mitochondrial dysfunction theory. Finally, we discuss the potential for future application of small fish model.

    DOI: 10.1007/s00702-017-1772-1

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  • Cerebrospinal fluid injection into adult zebrafish for disease research. 査読 国際誌

    Hideaki Matsui, Noriko Matsui

    Journal of neural transmission (Vienna, Austria : 1996)   124 ( 12 )   1627 - 1633   2017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)  

    DOI: 10.1007/s00702-017-1787-7

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  • The use of fish models to study human neurological disorders. 招待 査読 国際誌

    Hideaki Matsui

    Neuroscience research   120   1 - 7   2017年7月

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    担当区分:筆頭著者, 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)  

    DOI: 10.1016/j.neures.2017.02.004

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  • Dopamine system, cerebellum, and nucleus ruber in fish and mammals. 招待 査読

    Hideaki Matsui

    Development, growth & differentiation   59 ( 4 )   219 - 227   2017年5月

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    担当区分:筆頭著者, 最終著者, 責任著者   記述言語:英語  

    DOI: 10.1111/dgd.12357

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  • Analyzing Synaptic Modulation of Drosophila melanogaster Photoreceptors after Exposure to Prolonged Light. 査読 国際誌

    Atsushi Sugie, Christoph Möhl, Satoko Hakeda-Suzuki, Hideaki Matsui, Takashi Suzuki, Gaia Tavosanis

    Journal of visualized experiments : JoVE   ( 120 )   2017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)  

    DOI: 10.3791/55176

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  • An optimized method for counting dopaminergic neurons in zebrafish. 査読 国際誌

    Hideaki Matsui, Atsushi Sugie

    PloS one   12 ( 9 )   e0184363   2017年

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

    DOI: 10.1371/journal.pone.0184363

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  • Zebrafish jam-b2 Gal4-enhancer trap line recapitulates endogenous jam-b2 expression in extraocular muscles. 査読 国際誌

    Hideaki Matsui, Alessandro Dorigo, Astrid Buchberger, Jennifer C Hocking, Martin Distel, Reinhard W Köster

    Developmental dynamics : an official publication of the American Association of Anatomists   244 ( 12 )   1574 - 80   2015年12月

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    担当区分:筆頭著者   記述言語:英語  

    BACKGROUND: Members of the junctional adhesion molecule (JAM) family function as cell adhesion molecules and cell surface receptors. The zebrafish genome contains six different jam genes, and jam-b and jam-c were shown to be essential for myoblast fusion during skeletal muscle development. However, little is known about jam-b2 expression and function. RESULTS: We isolated the cDNA of zebrafish jam-b2. jam-b2 is expressed specifically in extraocular muscles (EOMs), jaw muscles, and pectoral fins in zebrafish larvae, but not in trunk muscles. The identified jam-b2 expression pattern is supported by the analysis of a zebrafish Gal4-enhancer trap line, in which the coding sequence of the transcriptional activator KalTA4 together with a Gal4-dependent UAS-mCherry expression cassette was inserted into the jam-b2 locus. Intercrosses with an UAS:EGFP strain proves the possibility for targeting transgene expression to EOMs, jaw muscles and fins. Finally, we characterized the concerted contraction pattern of EOMs in larvae performing an optokinetic response. CONCLUSIONS: The expression pattern of jam-b2 suggests that it may contribute different properties to EOMs, jaw muscles, and pectoral fins. The jam-b2:KalTA4-UAS-mCherry transgenic strain serves a dual role as both a reporter for these muscles and as a valuable genetic tool for targeting transgene expression to EOMs.

    DOI: 10.1002/dvdy.24347

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  • Viable neuronopathic Gaucher disease model in Medaka (Oryzias latipes) displays axonal accumulation of alpha-synuclein. 査読 国際誌

    Norihito Uemura, Masato Koike, Satoshi Ansai, Masato Kinoshita, Tomoko Ishikawa-Fujiwara, Hideaki Matsui, Kiyoshi Naruse, Naoaki Sakamoto, Yasuo Uchiyama, Takeshi Todo, Shunichi Takeda, Hodaka Yamakado, Ryosuke Takahashi

    PLoS genetics   11 ( 4 )   e1005065   2015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:4  

    Homozygous mutations in the glucocerebrosidase (GBA) gene result in Gaucher disease (GD), the most common lysosomal storage disease. Recent genetic studies have revealed that GBA mutations confer a strong risk for sporadic Parkinson's disease (PD). To investigate how GBA mutations cause PD, we generated GBA nonsense mutant (GBA-/-) medaka that are completely deficient in glucocerebrosidase (GCase) activity. In contrast to the perinatal death in humans and mice lacking GCase activity, GBA-/- medaka survived for months, enabling analysis of the pathological progression. GBA-/- medaka displayed the pathological phenotypes resembling human neuronopathic GD including infiltration of Gaucher cell-like cells into the brains, progressive neuronal loss, and microgliosis. Detailed pathological findings represented lysosomal abnormalities in neurons and alpha-synuclein (α-syn) accumulation in axonal swellings containing autophagosomes. Unexpectedly, disruption of α-syn did not improve the life span, formation of axonal swellings, neuronal loss, or neuroinflammation in GBA-/- medaka. Taken together, the present study revealed GBA-/- medaka as a novel neuronopathic GD model, the pahological mechanisms of α-syn accumulation caused by GCase deficiency, and the minimal contribution of α-syn to the pathogenesis of neuronopathic GD.

    DOI: 10.1371/journal.pgen.1005065

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  • Identification of the zebrafish red nucleus using Wheat Germ Agglutinin transneuronal tracing. 査読 国際誌

    Hideaki Matsui, Kazuhiko Namikawa, Reinhard W Köster

    Communicative & integrative biology   7 ( 6 )   e994383   2014年12月

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

    The red nucleus is located in the rostral midbrain of the vertebrate brain and controls motor coordination during locomotion. It receives input from the cerebellum and sends its output to the spinal cord. The presence of the red nucleus is well established in tetrapods, and its existence has also been suggested in teleosts but its presence and position has still been under discussion. By using wheat germ agglutinin (WGA) as a genetically encoded anterograde tracer, we recently identified contralateral projections from the cerebellum to a putative red nucleus in the zebrafish midbrain tegmentum. In this report we further revealed red nucleus derived from this contralateral afferent from the cerebellum using WGA and contralateral projections to the hindbrain-spinal cord junction site using DiI-mediated retrograde tracing. Thus the structure that we have identified by anterograde and retrograde tracing fulfills the anatomical demands for the red nucleus: the location in the midbrain tegmentum, contralateral afferent from the cerebellum (cerebello-ruber projection) and contralateral efferent to the spinal cord (rubro-spinal projection).

    DOI: 10.4161/19420889.2014.994383

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  • Neuronopathic Gaucher's disease model of medaka displayed axonal accumulation of alpha-synuclein 査読

    Uemura Norihito, Takahashi Ryosuke, Koike Masato, Kinoshita Masato, Fujiwara-Ishikawa Tomoko, Matsui Hideaki, Yamakado Hodaka, Uchiyama Yasuo, Todo Takeshi, Takeda Shun-ichi

    MOVEMENT DISORDERS   29   S64   2014年11月

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  • Functional regionalization of the teleost cerebellum analyzed in vivo. 査読 国際誌

    Hideaki Matsui, Kazuhiko Namikawa, Andreas Babaryka, Reinhard W Köster

    Proceedings of the National Academy of Sciences of the United States of America   111 ( 32 )   11846 - 51   2014年8月

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    担当区分:筆頭著者, 責任著者   記述言語:英語   出版者・発行元:32  

    There has been accumulating evidence for a regionalized organization of the cerebellum, which was mostly deduced from anatomical mapping of axonal projections of cerebellar afferents. A likewise regionalization of the cerebellar output has been suggested from lesion studies and dye-tracer experiments, but its physiological targets as well as the functional relevance of such an output regionalization are less clear. Ideally, such functional regionalization should be proven noninvasively in vivo. We here provide evidence for such a regionalization of the output from the cerebellar cortex by genetically encoded transneuronal mapping of efferent circuits of zebrafish Purkinje neurons. These identified circuits correspond to distinct regionalized Purkinje cell activity patterns in freely behaving zebrafish larvae during the performance of cerebellar-dependent behaviors. Furthermore, optogenetic interrogation of selected Purkinje cell regions during animal behavior confirms the functional regionalization of Purkinje cell efferents and reveals their contribution to behavior control as well as their function in controlling lateralized behavioral output. Our findings reveal how brain compartments serve to fulfill a multitude of functions by dedicating specialized efferent circuits to distinct behavioral tasks.

    DOI: 10.1073/pnas.1403105111

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  • Exploring the pathogenetic mechanisms underlying Parkinson's disease in medaka fish. 査読 国際誌

    Hideaki Matsui, Norihito Uemura, Hodaka Yamakado, Shunichi Takeda, Ryosuke Takahashi

    Journal of Parkinson's disease   4 ( 2 )   301 - 10   2014年

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    担当区分:筆頭著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:2  

    Teleost fish have recently been employed as a model for human neurodegenerative diseases. We used toxin exposure and genetic engineering to develop models of Parkinson's disease (PD) in the teleost fish, medaka. Among the toxins examined, 1-methyl-4-phenyl-1,2,3,4-tetrahydropyridine (MPTP), 6-hydroxydopamine (6-OHDA), proteasome inhibitors, lysosome inhibitors, and tunicamycin all induced important features of PD in medaka. Specifically, these agents induced dopaminergic cell loss and reduced spontaneous movement, and the latter three toxins produced inclusion bodies that were ubiquitously distributed in the medaka brain. Despite the extensive distribution of these inclusion bodies, the middle diencephalic dopaminergic neurons were particularly susceptible to the effect of the toxins, suggesting that this cluster of dopaminergic neurons is analogous to the human substantia nigra. We have also created a variety of different genetic models using the Targeting Induced Local Lesions in Genomes (TILLING) method, and found that neither PTEN-induced putative kinase 1 (PINK1) mutants nor Parkin mutants disclosed significant dopaminergic cell loss. Surprisingly however, PINK1 and Parkin double mutants exhibited selective dopamine cell loss, as well as aggregation and deficit of mitochondrial activity. Another mutant, the ATP13A2 mutant, also expressed a PD phenotype, exhibiting marked cathepsin D reduction and fingerprint-like structures that are generally found in lysosome storage diseases. Taken together, these data indicate that medaka fish can serve as a new animal model for PD. In this review, we summarize our data and discuss the potential for future application of this animal model.

    DOI: 10.3233/JPD-130289

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  • TigarB causes mitochondrial dysfunction and neuronal loss in PINK1 deficiency. 査読 国際誌

    Laura J Flinn, Marcus Keatinge, Sandrine Bretaud, Heather Mortiboys, Hideaki Matsui, Elena De Felice, Helen I Woodroof, Lucy Brown, Aimee McTighe, Rosemarie Soellner, Claire E Allen, Paul R Heath, Marta Milo, Miratul M K Muqit, Andreas S Reichert, Reinhard W Köster, Philip W Ingham, Oliver Bandmann

    Annals of neurology   74 ( 6 )   837 - 47   2013年12月

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    OBJECTIVE: Loss of function mutations in PINK1 typically lead to early onset Parkinson disease (PD). Zebrafish (Danio rerio) are emerging as a powerful new vertebrate model to study neurodegenerative diseases. We used a pink1 mutant (pink(-/-) ) zebrafish line with a premature stop mutation (Y431*) in the PINK1 kinase domain to identify molecular mechanisms leading to mitochondrial dysfunction and loss of dopaminergic neurons in PINK1 deficiency. METHODS: The effect of PINK1 deficiency on the number of dopaminergic neurons, mitochondrial function, and morphology was assessed in both zebrafish embryos and adults. Genome-wide gene expression studies were undertaken to identify novel pathogenic mechanisms. Functional experiments were carried out to further investigate the effect of PINK1 deficiency on early neurodevelopmental mechanisms and microglial activation. RESULTS: PINK1 deficiency results in loss of dopaminergic neurons as well as early impairment of mitochondrial function and morphology in Danio rerio. Expression of TigarB, the zebrafish orthologue of the human, TP53-induced glycolysis and apoptosis regulator TIGAR, was markedly increased in pink(-/-) larvae. Antisense-mediated inactivation of TigarB gave rise to complete normalization of mitochondrial function, with resulting rescue of dopaminergic neurons in pink(-/-) larvae. There was also marked microglial activation in pink(-/-) larvae, but depletion of microglia failed to rescue the dopaminergic neuron loss, arguing against microglial activation being a key factor in the pathogenesis. INTERPRETATION: Pink1(-/-) zebrafish are the first vertebrate model of PINK1 deficiency with loss of dopaminergic neurons. Our study also identifies TIGAR as a promising novel target for disease-modifying therapy in PINK1-related PD.

    DOI: 10.1002/ana.23999

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  • PINK1 and Parkin complementarily protect dopaminergic neurons in vertebrates. 査読 国際誌

    Hideaki Matsui, Roberto Gavinio, Takeshi Asano, Norihito Uemura, Hidefumi Ito, Yoshihito Taniguchi, Yoshito Kobayashi, Takakuni Maki, Jie Shen, Shunichi Takeda, Kengo Uemura, Hodaka Yamakado, Ryosuke Takahashi

    Human molecular genetics   22 ( 12 )   2423 - 34   2013年6月

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    担当区分:筆頭著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:12  

    Parkinson's disease (PD) is a common neurodegenerative disorder characterized by selective dopaminergic cell loss in the substantia nigra, but its pathogenesis remains unclear. The recessively inherited familial PD genes PARK2 and PARK6 have been attributed to mutations in the Parkin and PTEN-induced kinase 1 (PINK1) genes, respectively. Recent reports suggest that PINK1 works upstream of Parkin in the same pathway to regulate mitochondrial dynamics and/or conduct autophagic clearance of damaged mitochondria. This phenomenon is preserved from Drosophila to human cell lines but has not been demonstrated in a vertebrate animal model in vivo. Here, we developed a medaka fish (Oryzias latipes) model that is deficient in Pink1 and Parkin. We found that despite the lack of a conspicuous phenotype in single mutants for Pink1 or Parkin, medaka that are deficient in both genes developed phenotypes similar to that of human PD: late-onset locomotor dysfunction, a decrease in dopamine levels and a selective degeneration of dopaminergic neurons. Further analysis also revealed defects in mitochondrial enzymatic activity as well as cell death. Consistently, PINK1 and Parkin double-deficient MEF showed a further decrease in mitochondrial membrane potential and mitochondrial complex I activity as well as apoptosis compared with single-deficient MEF. Interestingly, these mitochondrial abnormalities in Parkin-deficient MEF were compensated by exogenous PINK1, but not by disease-related mutants. These results suggest that PINK1 and Parkin work in a complementary way to protect dopaminergic neurons by maintaining mitochondrial function in vertebrates.

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  • ATP13A2 deficiency induces a decrease in cathepsin D activity, fingerprint-like inclusion body formation, and selective degeneration of dopaminergic neurons. 査読 国際誌

    Hideaki Matsui, Fumiaki Sato, Shigeto Sato, Masato Koike, Yosuke Taruno, Shinji Saiki, Manabu Funayama, Hidefumi Ito, Yoshihito Taniguchi, Norihito Uemura, Atsushi Toyoda, Yoshiyuki Sakaki, Shunichi Takeda, Yasuo Uchiyama, Nobutaka Hattori, Ryosuke Takahashi

    FEBS letters   587 ( 9 )   1316 - 25   2013年5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:9  

    Kufor-Rakeb syndrome (KRS) was originally described as an autosomal recessive form of early-onset parkinsonism with pyramidal degeneration and dementia. ATP13A2 was identified as the causative gene in KRS. ATP13A2 encodes the ATP13A2 protein, which is a lysosomal type5 P-type ATPase, and ATP13A2 mutations are linked to autosomal recessive familial parkinsonism. Here, we report that normal ATP13A2 localizes in the lysosome, whereas disease-associated variants remain in the endoplasmic reticulum. Cathepsin D activity was decreased in ATP13A2-knockdown cells that displayed lysosome-like bodies characterized by fingerprint-like structures. Furthermore, an atp13a2 mutation in medaka fish resulted in dopaminergic neuronal death, decreased cathepsin D activity, and fingerprint-like structures in the brain. Based on these results, lysosome abnormality is very likely to be the primary cause of KRS/PARK9.

    DOI: 10.1016/j.febslet.2013.02.046

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  • Medaka fish Parkinson's disease model. 査読 国際誌

    Hideaki Matsui, Roberto Gavinio, Ryosuke Takahashi

    Experimental neurobiology   21 ( 3 )   94 - 100   2012年9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:3  

    The teleost fish has been widely used in creating neurodegenerative models. Here we describe the teleost medaka fish Parkinson's disease (PD) models we developed using toxin treatment and genetic engineering. 1-Methyl-4-phenyl-1,2,3,4-tetrahydropyridine (MPTP), 6-hydroxydopamine (6-OHDA), proteasome inhibitors, lysosome inhibitors and tunicamycin treatment in our model fish replicated some salient features of PD: selective dopamine cell loss and reduced spontaneous movement with the last three toxins producing inclusion bodies ubiquitously in the brain. Despite the ubiquitous distribution of the inclusion bodies, the middle diencephalic dopaminergic neurons were particularly vulnerable to these toxins, supporting the idea that this dopamine cluster is similar to the human substantia nigra. PTEN-induced putative kinase 1 (PINK1) homozygous mutants also showed reduced spontaneous swimming movements. These data indicate that medaka fish can serve as a new model animal of PD. In this review we summarize our previous data and discuss future prospects.

    DOI: 10.5607/en.2012.21.3.94

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  • Ammonium chloride and tunicamycin are novel toxins for dopaminergic neurons and induce Parkinson's disease-like phenotypes in medaka fish 査読

    Hideaki Matsui, Hidefumi Ito, Yoshihito Taniguchi, Shunichi Takeda, Ryosuke Takahashi

    JOURNAL OF NEUROCHEMISTRY   115 ( 5 )   1150 - 1160   2010年12月

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

    DOI: 10.1111/j.1471-4159.2010.07012.x

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  • Proteasome inhibition in medaka brain induces the features of Parkinson&apos;s disease 査読

    Hideaki Matsui, Hidefumi Ito, Yoshihito Taniguchi, Haruhisa Inoue, Shunichi Takeda, Ryosuke Takahashi

    JOURNAL OF NEUROCHEMISTRY   115 ( 1 )   178 - 187   2010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)  

    DOI: 10.1111/j.1471-4159.2010.06918.x

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  • Loss of PINK1 in medaka fish (Oryzias latipes) causes late-onset decrease in spontaneous movement 査読

    Hideaki Matsui, Yoshihito Taniguchi, Haruhisa Inoue, Yoshito Kobayashi, Yoshiyuki Sakaki, Atsushi Toyoda, Kengo Uemura, Daisuke Kobayashi, Shunichi Takeda, Ryosuke Takahashi

    NEUROSCIENCE RESEARCH   66 ( 2 )   151 - 161   2010年2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)  

    DOI: 10.1016/j.neures.2009.10.010

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  • A chemical neurotoxin, MPTP induces Parkinson&apos;s disease like phenotype, movement disorders and persistent loss of dopamine neurons in medaka fish 査読

    Hideaki Matsui, Yoshihito Taniguchi, Haruhisa Inoue, Kengo Uemura, Shunichi Takeda, Ryosuke Takahashi

    NEUROSCIENCE RESEARCH   65 ( 3 )   263 - 271   2009年11月

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

    DOI: 10.1016/j.neures.2009.07.010

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  • Depression in Parkinson's disease - Diffusion tensor imaging study 査読

    Hideaki Matsui, Kazuto Nishinaka, Masaya Oda, Hidekazu Niikawa, Kenichi Komatsu, Tamotsu Kubori, Fukashi Udaka

    JOURNAL OF NEUROLOGY   254 ( 9 )   1170 - 1173   2007年9月

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

    DOI: 10.1007/s00415-006-0236-6

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  • Dementia in Parkinson's disease: diffusion tensor imaging 査読

    H. Matsui, K. Nishinaka, M. Oda, H. Niikawa, T. Kubori, F. Udaka

    ACTA NEUROLOGICA SCANDINAVICA   116 ( 3 )   177 - 181   2007年9月

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

    DOI: 10.1111/j.1600-0404.2007.00838.x

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  • Wisconsin card, sorting test in Parkinson's disease: diffusion tensor imaging 査読

    H. Matsui, K. Nishinaka, M. Oda, H. Niikawa

    ACTA NEUROLOGICA SCANDINAVICA   116 ( 2 )   108 - 112   2007年8月

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

    DOI: 10.1111/j.1600-0404.2006.00795.x

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  • Trousseau syndrome due to pleural mesothelioma 査読

    Hideaki Matsui, Kazuto Nishinaka, Masaya Oda, Tamotsu Kubori, Fukashi Udaka

    NEUROLOGIST   13 ( 4 )   205 - 208   2007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)  

    DOI: 10.1097/01.nrl.0000253113.53846.ec

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  • Heterogeneous factors in dementia with Parkinson's disease: IMP-SPECT study 査読

    Hideaki Matsui, Kazuto Nishinaka, Masaya Oda, Narihiro Hara, Kenichi Komatsu, Tamotsu Kubori, Fukashi Udaka

    PARKINSONISM & RELATED DISORDERS   13 ( 3 )   174 - 181   2007年

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

    DOI: 10.1016/j.parkreldis.2006.10.005

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  • Thalamic hyperperfusion in verbal hallucination of parkinsonian patients 査読

    Hideaki Matsui, Kazuto Nishinaka, Takafumi Miyoshi, Narihiro Hara, Masaya Oda, Tamotsu Kubori, Fukashi Udaka

    INTERNAL MEDICINE   46 ( 21 )   1765 - 1769   2007年

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

    DOI: 10.2169/internalmedicine.46.0191

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  • Auditory event-related potentials in Parkinson's disease: Prominent correlation with attention 査読

    Hideaki Matsui, Kazuto Nishinaka, Masaya Oda, Tamotsu Kubori, Fukashi Udaka

    PARKINSONISM & RELATED DISORDERS   13 ( 7 )   394 - 398   2007年

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

    DOI: 10.1016/j.parkreldis.2006.12.012

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  • Adult onset hemiparkinsonism with brain hemihypoplasia 査読

    Hideaki Matsui, Kazuto Nishinaka, Masaya Oda, Kenichi Komatsu, Tamotsu Kubori, Fukashi Udaka

    NEUROLOGY INDIA   54 ( 4 )   450 - 451   2006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  

    DOI: 10.4103/0028-3886.28136

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  • Hypoperfusion of the auditory and prefrontal cortices in parkinsonian patients with verbal hallucinations 査読

    Hideaki Matsui, Kazuto Nishinaka, Masaya Oda, Narihiro Hara, Kenichi Komatsu, Tamotsu Kubori, Fukashi Udaka

    MOVEMENT DISORDERS   21 ( 12 )   2165 - 2169   2006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)  

    DOI: 10.1002/mds.21147

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  • Hypoperfusion of the visual pathway in parkinsonian patients with visual hallucinations 査読

    Hideaki Matsui, Kazuto Nishinaka, Masaya Oda, Narihiro Hara, Kenichi Komatsu, Tamotsu Kubori, Fukashi Udaka

    MOVEMENT DISORDERS   21 ( 12 )   2140 - 2144   2006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)  

    DOI: 10.1002/mds.21140

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  • Minor depression and brain perfusion images in Parkinson's disease 査読

    Hideaki Matsui, Kazuto Nishinaka, Masaya Oda, Kenichi Komatsu, Tamotsu Kubori, Fukashi Udaka

    MOVEMENT DISORDERS   21 ( 8 )   1169 - 1174   2006年8月

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

    DOI: 10.1002/mds.20923

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  • Excessive daytime sleepiness in Parkinson disease: A SPECT study 査読

    Hideaki Matsui, Kazuto Nishinaka, Masaya Oda, Narihiro Hara, Kenichi Komatsu, Tamotsu Kubori, Fukashi Udaka

    SLEEP   29 ( 7 )   917 - 920   2006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)  

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  • Frontal assessment battery and brain perfusion image in Parkinson's disease 査読

    H Matsui, F Udaka, T Miyoshi, N Hara, A Tamura, M Oda, T Kubori, K Nishinaka, M Kameyama

    JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY   19 ( 1 )   41 - 45   2006年3月

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

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  • Encephalopathy and severe neuropathy due to probable systemic vasculitis as an initial manifestation of mixed connective tissue disease 査読

    H Matsui, F Udaka, M Oda, T Kubori, K Nishinaka, M Kameyama

    NEUROLOGY INDIA   54 ( 1 )   83 - 85   2006年3月

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

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  • HTLV-I-associated peripheral neuropathy with smoldering-type adult T-cell leukemia 査読

    H Matsui, F Udaka, T Kubori, M Oda, K Nishinaka, N Oka

    NEUROLOGIST   12 ( 2 )   109 - 113   2006年3月

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

    DOI: 10.1097/01.nrl.0000202598.81422.36

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  • Impaired visual acuity as a risk factor for visual hallucinations in Parkinson's disease 査読

    H Matsui, F Udaka, A Tamura, M Oda, T Kubori, K Nishinaka, M Kameyama

    JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY   19 ( 1 )   36 - 40   2006年3月

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

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  • Wisconsin Card Sorting Test and brain perfusion imaging in Parkinson's disease 査読

    H Matsui, K Nishinaka, M Oda, N Hara, K Komatsu, T Kubori, F Udaka

    PARKINSONISM & RELATED DISORDERS   12 ( 5 )   273 - 278   2006年

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

    DOI: 10.1016/j.parkreldis.2005.12.006

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  • Parkinson's disease following panic disorder 査読

    Hideaki Matsui, Fukashi Udaka, Masaya Oda, Akiko Tamura, Tamotsu Kubori, Kazuto Nishinaka, Masakuni Kameyama

    Journal of Neuropsychiatry and Clinical Neurosciences   18 ( 1 )   130   2006年

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    担当区分:筆頭著者, 責任著者   記述言語:英語   出版者・発行元:American Psychiatric Publishing Inc.  

    DOI: 10.1176/jnp.18.1.130

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  • A case of Parkinson's disease with L-dopa-evoked catalepsy 査読

    Hirohide Asai, Fukashi Udaka, Naoya Oishi, Masaya Oda, Hideaki Matsui, Tamotsu Kubori, Kazuto Nishinaka, Yoshiko Furiya, Satoshi Ueno, Masakuni Kameyama

    PARKINSONISM & RELATED DISORDERS   12   S91 - S91   2006年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.parkreldis.2006.05.020

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  • Disruptions of the fornix fiber in parkinsonian patients with excessive daytime sleepiness 査読

    H Matsui, K Nishinaka, M Oda, H Niikawa, K Komatsu, T Kubori, F Udaka

    PARKINSONISM & RELATED DISORDERS   12 ( 5 )   319 - 322   2006年

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  • Does cardiac metaiodobenzylguanidine (MIBG) uptake in Parkinson's disease correlate with major autonomic symptoms? 査読

    H Matsui, K Nishinaka, M Oda, K Komatsu, T Kubori, F Udaka

    PARKINSONISM & RELATED DISORDERS   12 ( 5 )   284 - 288   2006年

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

    DOI: 10.1016/j.parkreldis.2005.12.008

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  • Three-dimensional stereotactic surface projection study of freezing of gait and brain perfusion image in Parkinson's disease 査読

    H Matsui, F Udaka, T Miyoshi, N Hara, A Tamaura, M Oda, T Kubori, K Nishinaka, M Kameyama

    MOVEMENT DISORDERS   20 ( 10 )   1272 - 1277   2005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)  

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  • N-isopropyl-p-I-123 iodoamphetamine single photon emission computed tomography study of Parkinson's disease with dementia 査読

    H Matsui, F Udaka, T Miyoshi, N Hara, A Tamura

    INTERNAL MEDICINE   44 ( 10 )   1046 - 1050   2005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)  

    DOI: 10.2169/internalmedicine.44.1046

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  • Multiple sclerosis following splenectomy as a treatment for idiopathic thrombocytopenic purpura 査読

    H Matsui, F Udaka, A Tamura, M Oda, T Kubori, K Nishinaka, M Kameyama

    INTERNAL MEDICINE   44 ( 7 )   747 - 749   2005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)  

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  • Three-dimensional stereotactic surface projection study of orthostatic hypotension and brain perfusion image in Parkinson's disease 査読

    H Matsui, F Udaka, T Miyoshi, N Hara, A Tamura, M Oda, T Kubori, K Nishinaka, M Kameyama

    ACTA NEUROLOGICA SCANDINAVICA   112 ( 1 )   36 - 41   2005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)  

    DOI: 10.1111/j.1600-0404.2005.00427.x

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  • Brain perfusion differences between Parkinson's disease and multiple system atrophy with predominant parkinsonian features 査読

    H Matsui, F Udaka, T Miyoshi, N Hara, A Tamura, M Oda, T Kubori, K Nishinaka, M Kameyama

    PARKINSONISM & RELATED DISORDERS   11 ( 4 )   227 - 232   2005年6月

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

    DOI: 10.1016/j.parkreldis.2005.01.001

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  • Metaiodobenzylguanidine (MIBG) uptake in Parkinson's disease also decreases at thyroid 査読

    H Matsui, F Udaka, M Oda, A Tamura, T Kubori, K Nishinaka, M Kameyama

    ANNALS OF NUCLEAR MEDICINE   19 ( 3 )   225 - 229   2005年5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)  

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  • Persistent primitive hypoglossal artery with atrial septal defect 査読

    H Matsui, F Udaka, T Kubori, M Oda, K Nishinaka, M Kameyama

    INTERNAL MEDICINE   44 ( 5 )   507 - 508   2005年5月

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

    DOI: 10.2169/internalmedicine.44.507

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  • Metaiodobenzylguanidine (MIBG) scintigraphy at various parts of the body in Parkinson's disease and multiple system atrophy 査読

    H Matsui, F Udaka, M Oda, T Kubori, K Nishinaka, M Kameyama

    AUTONOMIC NEUROSCIENCE-BASIC & CLINICAL   119 ( 1 )   56 - 60   2005年4月

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

    DOI: 10.1016/j.autneu.2005.03.003

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  • The relation between visual hallucinations and visual evoked potential in Parkinson disease 査読

    H Matsui, F Udaka, A Tamura, M Oda, T Kubori, K Nishinaka, M Kameyama

    CLINICAL NEUROPHARMACOLOGY   28 ( 2 )   79 - 82   2005年3月

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    担当区分:筆頭著者, 責任著者   記述言語:英語  

    DOI: 10.1097/01.wnf.0000157066.50948.65

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  • POEMS syndrome demonstrating VEGF decrease by ticlopidine 査読

    H Matsui, F Udaka, T Kubori, M Oda, K Nishinaka, M Kameyama

    INTERNAL MEDICINE   43 ( 11 )   1082 - 1083   2004年11月

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

    DOI: 10.2169/internalmedicine.43.1082

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  • Two cases of Parkinson's disease in which visual hallucinations disappeared after cataract surgery 査読

    Hideaki Matsui, Fukashi Udaka, Masaya Oda, Tamotsu Kubori, Kazuto Nishinaka, Masakuni Kameyama

    Brain and Nerve   56 ( 4 )   351 - 354   2004年4月

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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(学術雑誌)  

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▶ 全件表示

MISC

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講演・口頭発表等

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受賞

  • 学長賞

    2021年   新潟大学  

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  • 学長賞

    2020年   新潟大学  

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  • 日本神経科学学会奨励賞

    2016年   日本神経科学学会   小型魚類を用いた神経精神疾患研究

    松井 秀彰

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  • 研究教授

    2016年   新潟大学  

    松井 秀彰

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  • Alexander von Humboldt Fellowship

    2011年1月   Alexander von Humboldt Foundation  

    松井秀彰

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  • Best Poster Award

    2005年8月   パーキンソン病フォーラム   パーキンソン病におけるすくみ足と脳血流の関連

    松井 秀彰

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共同研究・競争的資金等の研究

  • 老化・疾患をもたらす各種の細胞質DNAに対するセンサーと細胞応答の比較解析

    研究課題/領域番号:24K08826

    2024年4月 - 2027年3月

    制度名:科学研究費助成事業

    研究種目:基盤研究(C)

    提供機関:日本学術振興会

    酒井 晶子, 松井 秀彰

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    配分額:4550000円 ( 直接経費:3500000円 、 間接経費:1050000円 )

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  • 老化における細胞外廃棄の生理学、およびその破綻による加齢関連疾患の病態生理学

    2023年10月 - 2029年3月

    制度名:革新的先端研究開発支援事業

    研究種目:AMED-CREST

    提供機関:AMED

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    担当区分:研究代表者 

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  • APPとαシヌクレインの生理機能に立脚したアルツハイマーとパーキンソンのシン病態

    研究課題/領域番号:23K17421

    2023年6月 - 2026年3月

    制度名:科学研究費助成事業

    研究種目:挑戦的研究(開拓)

    提供機関:日本学術振興会

    松井 秀彰

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    配分額:26000000円 ( 直接経費:20000000円 、 間接経費:6000000円 )

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  • 異所性のDNAがもたらす老化・加齢関連疾患・感染症病態の網羅的比較解析

    研究課題/領域番号:22H00501

    2022年4月 - 2027年3月

    制度名:科学研究費助成事業

    研究種目:基盤研究(A)

    提供機関:日本学術振興会

    松井 秀彰, 垣花 太一, 渡邉 香奈子

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    配分額:41860000円 ( 直接経費:32200000円 、 間接経費:9660000円 )

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  • 自律神経調節による非アルコール性脂肪性肝疾患の治療への基盤研究

    研究課題/領域番号:21K19478

    2021年7月 - 2024年3月

    制度名:科学研究費助成事業

    研究種目:挑戦的研究(萌芽)

    提供機関:日本学術振興会

    寺井 崇二, 上村 顕也, 上野 将紀, 松井 秀彰

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    配分額:6500000円 ( 直接経費:5000000円 、 間接経費:1500000円 )

    本研究では、NASHにおける自律神経が繋ぐ多臓器連関の仕組みを解明し、その調節によってNASHの治療法を開発することを目的としている。
    今年度は、NASHの病態と自律神経が繋ぐ多臓器連関を解明するために、視床下部の4型メラノコルチン受容体(MC4R)のノックアウトマウス、高脂肪食給餌マウス、メチオニンコリン欠乏食給餌マウスをNASHモデルマウスとして、経時的な病態変化に伴う自律神経系のシグナル伝達と肝臓、脳、消化管における液性因子を検証した。
    また、多臓器の連関を検討する目的で、メダカ高脂肪食給餌によるNASHモデルでの心臓、腎臓での組織学的検証と種々の代謝経路を標的とした治療法による改善効果を検討し、自律神経経路を介したNASHの治療標的の検討を行った。

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  • 臓器連関の包括的理解に基づく認知症関連疾患の克服に向けて

    2021年4月

    制度名:ムーンショット目標2

    提供機関:JST

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  • ミトコンドリアDNAの漏出が起こす個体機能低下及び諸臓器の加齢関連疾患の解析

    2019年10月 - 2023年3月

    制度名:革新的先端研究開発支援事業PRIME

    提供機関:AMED

    松井 秀彰

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    担当区分:研究代表者  資金種別:競争的資金

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  • 異所性のミトコンドリアDNAを処理することによる二大認知症の治療探索

    2019年9月 - 2021年3月

    制度名:脳科学研究戦略推進プログラム

    提供機関:AMED

    松井 秀彰

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    担当区分:研究代表者  資金種別:競争的資金

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  • 異所性のミトコンドリアDNAがもたらす神経変性

    研究課題/領域番号:18H02716

    2018年4月 - 2021年3月

    制度名:科学研究費助成事業 基盤研究(B)

    研究種目:基盤研究(B)

    提供機関:日本学術振興会

    松井 秀彰

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    配分額:17550000円 ( 直接経費:13500000円 、 間接経費:4050000円 )

    申請者らは約5ヶ月という脊椎動物で最短の寿命を持ち、かつ最速で老化するアフリカメダカ(N. furzeri)が、その短いライフコースの間に加齢とともにパーキンソン病の表現型を呈することを報告した(Matsui et al., Cell Reports, 2019)。アフリカメダカではパーキンソン病において蓄積するαシヌクレインを遺伝子編集で除去すると、パーキンソン病の表現型が改善するものの、脳以外の諸臓器は通常通り老化が進行する(Matsui et al., Cell Reports, 2019)。すなわち全身の老化と加齢関連疾患(この場合パーキンソン病)を分離することができる。核DNAの細胞質漏出と強い関連を持つ老化現象と、各臓器やシステムで引き起こされる加齢関連疾患は、完全には同じメカニズムで起こっているのではなくある程度分離可能な現象であると言える。
    そのアフリカメダカおよびこれまでに作製解析した様々なパーキンソン病モデル、ヒト剖検脳症例を検討し、それらに共通の病態: 脳において『加齢とともにmtDNAが細胞質に漏出し細胞死を惹起する』可能性を見出した。具体的にはパーキンソン病モデルの小型魚類や培養細胞では細胞質にmtDNAが漏出し、タイプⅠインターフェロン(type I IFN)反応の亢進、細胞死を認める。Youle博士のグループからもPINK1/Parkin遺伝子改変のパーキンソン病マウスモデルにおいて、細胞質におけるDNA感知のkey分子の一つであるSTINGがその細胞死に関与していること、血液中にmtDNAが増加していることが報告されている(Sliter et al., Nature, 2018)。申請者らはさらにヒトパーキンソン病剖検脳においてもmtDNAが蓄積していること、細胞質DNAセンサーであるある蛋白が著増していることを報告中である。

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  • 超短命アフリカメダカで明らかにするパーキンソン病の新たな病態

    2018年

    制度名:ビジョナリーリサーチ継続助成(ステップ)

    提供機関:武田科学振興財団

    松井 秀彰

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    担当区分:研究代表者  資金種別:競争的資金

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  • αシヌクレイン老化が引き起こす個体老化パーキンソン病

    2017年4月 - 2019年3月

    制度名:新学術領域研究(研究領域提案型)

    提供機関:文部科学省

    松井 秀彰

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    担当区分:研究代表者  資金種別:競争的資金

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  • αシヌクレイン老化が引き起こす個体老化パーキンソン病

    研究課題/領域番号:17H05692

    2017年4月 - 2019年3月

    制度名:科学研究費助成事業 新学術領域研究(研究領域提案型)

    研究種目:新学術領域研究(研究領域提案型)

    提供機関:日本学術振興会

    松井 秀彰

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    配分額:10660000円 ( 直接経費:8200000円 、 間接経費:2460000円 )

    パーキンソン病(PD)はその発症に老化が強く関連しています。モザンビークに棲息するアフリカメダカは脊椎動物で現在最も短命でありながら非常に早期に老化の兆候を呈します。この約5ヶ月で短い一生を終えるサイクルは内因的なもので、このサイクルは野生のみならず実験室内でも再現されます。さらに加齢に伴い、臓器の萎縮、運動能力の低下、脊柱彎曲、癌の発生頻度の上昇、テロメアの短縮、老化関連酸性β-ガラクトシダーゼの上昇など、老化の様々な兆候を示します。私達は”寿命最短・最速老化”脊椎動物=アフリカメダカが加齢によりヒトPDに類似した病態を呈するかどうかを検討しました。その結果この老化が抑制されない魚の中で、加齢以外なんら特別な処置なしに、ヒトPDに酷似した病変が進んでいくことを見いだしました。すなわちアフリカメダカは加齢依存性にドパミン・ノルアドレナリン神経の変性を示し、αシヌクレイン陽性の凝集体病変は神経系の局所から全中枢神経へ連続的に進展を見せました。またアフリカメダカのαシヌクレインはヒトαシヌクレインに対する伝搬性を持っていました。さらにアフリカメダカにおけるドパミン・ノルアドレナリン神経の変性は加齢及びαシヌクレイン依存性でした。今後はさらにアフリカメダカで知見を累積し、それをマウスやヒトにあてはめ、ヒトにおいても同様に、疾患発症初期あるいは発症前に、パーキンソン病の発症を抑止できるかどうかを臨床的に検討するに十分なエビデンスを得ます。またαシヌクレインの伝搬様式および細胞変性のメカニズムを明らかにすることでPD病変の開始・伝搬および進行・細胞変性、その全ての段階での治療介入を目指します。

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  • 実験動物アフリカメダカ:老化が抑制されないその魚は自然にパーキンソン病を発症する

    2016年4月 - 2018年3月

    制度名:挑戦的萌芽研究

    提供機関:文部科学省

    松井 秀彰

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    担当区分:研究代表者  資金種別:競争的資金

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  • 実験動物アフリカメダカ:老化が抑制されないその魚は自然にパーキンソン病を発症する

    研究課題/領域番号:16K14597

    2016年4月 - 2018年3月

    制度名:科学研究費助成事業

    研究種目:挑戦的萌芽研究

    提供機関:日本学術振興会

    松井 秀彰

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    配分額:3770000円 ( 直接経費:2900000円 、 間接経費:870000円 )

    超短命のアフリカメダカが加齢のみでパーキンソン病になることを示し、パーキンソン病の病態の解析に利用した。アフリカメダカのαシヌクレインはヒトαシヌクレインに対する伝搬性を持っていた。延髄―脊髄接合部レベルでの神経切断やαシヌクレインのKOといった処置を行うと、アフリカメダカのドパミン・ノルアドレナリン神経変性は改善された。

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  • 超短命アフリカメダカは神経疾患モデルとなり得るか?

    2016年

    制度名:ビジョナリーリサーチ継続助成(ホップ)

    提供機関:武田科学振興財団

    松井 秀彰

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    担当区分:研究代表者  資金種別:競争的資金

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  • シナプス機能indicatorを用いたin vivo imagingの展開

    研究課題/領域番号:15H05571

    2015年4月 - 2018年3月

    制度名:科学研究費助成事業

    研究種目:若手研究(A)

    提供機関:日本学術振興会

    松井 秀彰

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    担当区分:研究代表者  資金種別:競争的資金

    配分額:22100000円 ( 直接経費:17000000円 、 間接経費:5100000円 )

    本研究ではシナプス後膜に存在するAMPA型受容体を特異的に可視化することにより、シナプスの可塑的かつ動的な機能変化を生体で観察および解析可能にすることを目的とした。神経初代培養細胞を使ったchemical LTPやchemical LTDに対して、我々が作成したindicatorはそれぞれシグナル上昇、減少を呈した。現在は海馬スライスとゼブラフィッシュin vivoにおける応用を継続中である。

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  • 超短命アフリカメダカは神経精神疾患モデルとなり得るか?

    研究課題/領域番号:26640061

    2014年4月 - 2016年3月

    制度名:科学研究費助成事業

    研究種目:挑戦的萌芽研究

    提供機関:日本学術振興会

    松井 秀彰

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    担当区分:研究代表者  資金種別:競争的資金

    配分額:4030000円 ( 直接経費:3100000円 、 間接経費:930000円 )

    本研究では超短命の脊椎動物であるアフリカメダカにおいて加齢以外になんら特別な処置なしに、ヒトパーキンソン病に酷似した病変が進んでいくことを見いだしました。すなわちアフリカメダカは加齢依存性に神経変性およびαシヌクレイン陽性の凝集体の進展を示しました。これはまさにヒトパーキンソン病病理に瓜二つと言えます。

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  • 小型魚類を用いたシナプス可塑性のin vivoイメージング

    2013年8月 - 2015年3月

    制度名:研究活動スタート支援

    提供機関:文部科学省

    松井 秀彰

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    担当区分:研究代表者  資金種別:競争的資金

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  • 小型魚類を用いたシナプス可塑性のin vivoイメージング

    研究課題/領域番号:25890015

    2013年8月 - 2015年3月

    制度名:科学研究費助成事業 研究活動スタート支援

    研究種目:研究活動スタート支援

    提供機関:日本学術振興会

    松井 秀彰

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    配分額:1560000円 ( 直接経費:1200000円 、 間接経費:360000円 )

    AMPA-Rは、長期増強(Long-term potentiation: LTP)において、シナプス後膜においてその数が増加することが指摘されており、実際にシナプス可塑性の主要な一因を果たしていると考えられている。その数の増加は、同受容体の細胞内から細胞外への挿入とそれに続く側方拡散によってシナプス後膜に集積することによってなされる。つまりシナプス後膜に特異的に集簇したAMPA-Rを標識することでシナプス可塑性をモニターすることが可能である。
    そのためにシナプス後膜に存在し、AMPA-Rと複合体を形成するタンパク質PSD-95を利用した。PSD95の近傍にあるAMPA-Rのみを可視化することができれば、シナプス後膜特異的にAMPA-Rを半定量することが可能である。特定部位で切断したVenusの断片をそれぞれAMPA-R とPSD95 に結合させたものを作製し、HEK細胞やラットの初代神経細胞にそれらを共発現させた。AMPA-RとPSD95が近傍に位置し複合体を形成すれば、Venusタンパクが再構築され蛍光を発するはずである。
    初年度はHEK細胞ならびにラット神経初代培養細胞を用いて、chemical LTDおよびchemical LTPにてこのシステムが働くことを確認した。具体的にはsplit Venusを付属させたAMPA-RとPSD-95が神経細胞内で正常なlocalizationをとること、また両者がcolocalizationする箇所のみVenusの信号が確認される事を確認した。さらにVenusの切断部位を様々に検討し、LTDおよびLTPの同定に最適な切断部位を同定した。その結果chemical LTDおよびchemical LTPに対して鋭敏に反応する組み合わせを見いだす事に成功した。現在はゼブラフィッシュの樹立中である。

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担当経験のある授業科目(researchmap)

  • 医科学

    機関名:新潟大学

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  • 発生学

    機関名:TU Braunschweig

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  • 病気とその原因

    機関名:新潟大学

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  • 神経変性疾患

    機関名:TU Braunschweig

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担当経験のある授業科目

  • 先端医科学研究概説

    2023年
    機関名:新潟大学