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Exploring the novel role of mitochondrial dynamics in schizophrenia

Research Project

Project/Area Number 19K08041
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 52030:Psychiatry-related
Research InstitutionWakayama Medical University (2022-2023)
University of Fukui (2019-2021)

Principal Investigator

Keiko Iwata  和歌山県立医科大学, 薬学部, 講師 (30415088)

Co-Investigator(Kenkyū-buntansha) 松崎 秀夫  福井大学, 子どものこころの発達研究センター, 教授 (00334970)
Project Period (FY) 2019-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywordsmitochondria / oligodendrocyte / differentiaion / schizophrenia / oligodendrocye
Outline of Research at the Start

Abnormal energy metabolisms are reported in brains of schizophrenia (SZ). Mitochondria have a central role in energy metabolisms and significant reduction of mitochondria mass in oligodendrocytes have been observed in SZ brains. PGC-1 alpha is a key regulator of mitochondrial biogenesis. In a set of preliminary experiments, we hypothesize that PGC-1 alpha plays a crucial role in oligodendrocyte differentiation via regulating mitochondrial biogenesis and involved in pathophysiology of SZ. Here, we propose our project to verify this hypothesis.

Outline of Final Research Achievements

We identified the novel variant of PGC-1alpha, a transcriptional coactivator, which is a key regulator of mitochondrial biogenesis and was involved in oligodendrocyte differentiation using the human oligodendrocyte cell line. The variant was expressed in the human brain. We performed RNA sequences using human brain samples. (The study was Fukui University Medical Research Ethics Committee (approval no.2020028).) The expression of the variant was correlated with 2 transcriptional receptors which were involved in cell differentiation. We established the primary culture system of oligodendrocytes at Wakayama Medical Univ and confirmed that the expression of the novel variant was increased during the differentiation of the mouse oligodendrocyte precursor cells.

Academic Significance and Societal Importance of the Research Achievements

本研究は、中枢神経系の発達に関連する脳科学の分野にとって重要であるだけでなく、精神疾患の生物学的基盤を理解する上でも重要である。長年にわたり、神経細胞とシナプスが神経科学の主要な焦点となっており、精神疾患の病態生理に関する理論に影響を与えてきた。しかし脳内の細胞の大部分は神経細胞ではなく、グリア細胞である。本研究では、ミトコンドリアによって制御されるオリゴデンドロサイトの分化が、高次脳機能や統合失調症の病態生理にどのように影響するかに焦点を当てた。本研究で得られた結果は、統合失調症を含む精神疾患の病因・病態解明の一助になる可能性がある。

Report

(6 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (17 results)

All 2024 2023 2022 2021 2019 Other

All Int'l Joint Research (8 results) Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Open Access: 2 results) Presentation (5 results) (of which Int'l Joint Research: 1 results) Remarks (1 results)

  • [Int'l Joint Research] University of Padua(イタリア)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] Veneto Institute of Molecular Medicine/University of Padova(イタリア)

    • Related Report
      2022 Research-status Report
  • [Int'l Joint Research] Veneto Institute of Molecular Medicine/University of Padova(イタリア)

    • Related Report
      2021 Research-status Report
  • [Int'l Joint Research] University of Graz(オーストリア)

    • Related Report
      2021 Research-status Report
  • [Int'l Joint Research] University of Padua/VIMM(イタリア)

    • Related Report
      2020 Research-status Report
  • [Int'l Joint Research] University of Graz(オーストリア)

    • Related Report
      2020 Research-status Report
  • [Int'l Joint Research] University of Padua/VIMM(イタリア)

    • Related Report
      2019 Research-status Report
  • [Int'l Joint Research] University of Graz(オーストリア)

    • Related Report
      2019 Research-status Report
  • [Journal Article] Measurement of Mitochondrial Respiration in Cryopreserved Human Peripheral Blood Mononuclear Cells (PBMCs)2022

    • Author(s)
      Iwata Keiko、Xie Min-Jue、Guest Paul C.、Hirai Takaharu、Matsuzazki Hideo
    • Journal Title

      Methods Mol Biol.

      Volume: 2511 Pages: 321-332

    • DOI

      10.1007/978-1-0716-2395-4_24

    • ISBN
      9781071623947, 9781071623954
    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Autistic-Like Behavior and Impairment of Serotonin Transporter and AMPA Receptor Trafficking in N-Ethylmaleimide Sensitive Factor Gene-Deficient Mice2021

    • Author(s)
      Xie Min-Jue、Iwata Keiko、Ishikawa Yasuyuki、Nomura Yuki、Tani Tomomi、Murata Koshi、Fukazawa Yugo、Matsuzaki Hideo
    • Journal Title

      Frontiers in Genetics

      Volume: 12 Pages: 748627-748627

    • DOI

      10.3389/fgene.2021.748627

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dietary spermidine improves cognitive function2021

    • Author(s)
      Schroeder S, Hofer SJ, Zimmermann A, Pechlaner R, Dammbrueck C, Pendl T, Marcello GM, Pogatschnigg V, Bergmann M, Muller M, Gschiel V, Ristic S, Tadic J, Iwata K,......Racz B, Kiechl S, Eisenberg T, Madeo F.
    • Journal Title

      Cell Reports

      Volume: 35 Issue: 2 Pages: 108985-108985

    • DOI

      10.1016/j.celrep.2021.108985

    • Related Report
      2021 Research-status Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] The Role of mitochondria dynamics in oligodendrocyte differentiation2024

    • Author(s)
      Keiko Iwata,Hideo Matsuzaki,Masahumi Moguchi,Norihito Shintani
    • Organizer
      The 144th Annual Meeting of the Pharmaceutical Society of Japan
    • Related Report
      2023 Annual Research Report
  • [Presentation] Involvement of mitochondria dynamics in oligodendrocyte differentiation2023

    • Author(s)
      Keiko Iwata,Hideo Matsuzaki,Masahumi Moguchi,Norihito Shintani
    • Organizer
      The 64th Annual Meeting of the Japanese Society of Neuropathology /The 66th Annual Meeting of the Japanese Society of Neurochemistry
    • Related Report
      2023 Annual Research Report
  • [Presentation] 神経系の細胞分化における ミトコンドリアダイナミクスの役割2023

    • Author(s)
      岩田圭子, 松﨑秀夫, 新谷紀人
    • Organizer
      第11回ニューロカンファレンス和歌山
    • Related Report
      2022 Research-status Report
  • [Presentation] Exploring the novel role of mitochondria dynamics in neuron and oligodendrocyte differentiation.2022

    • Author(s)
      Keiko Iwata,Hideo Matsuzaki,Masahumi Moguchi,Norihito Shintani
    • Organizer
      第96回日本薬理学会年会
    • Related Report
      2022 Research-status Report
  • [Presentation] Exploring the novelrole of mitochondrialdynamics inschizophrenia.2019

    • Author(s)
      Iwata K, Matsuzaki H, Scorrano L
    • Organizer
      1st Scientific Symposium on Mitochondrial Biology
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Remarks] researchmap

    • URL

      https://researchmap.jp/keikoiwata

    • Related Report
      2022 Research-status Report

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Published: 2019-04-18   Modified: 2025-01-30  

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