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Neural homology of major depressive disorder between human and mouse

Research Project

Project/Area Number 20K07960
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 52030:Psychiatry-related
Research InstitutionNihon University

Principal Investigator

O'HASHI Kazunori  日本大学, 歯学部, 助教 (90617458)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2021: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2020: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Keywordsストレス / うつ / イメージング / うつ病 / マウス / 光学イメージング / 内側前頭前野
Outline of Research at the Start

あらゆる疾患モデルにおいて病態の生物学的基盤の再現は不可欠である。現行のうつモデルマウスは行動の表面妥当性は有するが、疾患に対する構成的妥当性が満たされていない。本研究は脳の相同性を利用し、うつ患者とうつマウスの脳活動が同じ神経活動基盤を持つことを示すことで、不完全なうつモデルマウスに疾患に関する構成的妥当性を付与し、臨床研究と同水準のうつ病態の特徴をモデル動物が備えていることを実証する。本研究成果は基礎と臨床に神経活動という共通のうつ病態基盤を提供することにつながり、今後のトランスレーショナルリサーチを推進することが期待できる。

Outline of Final Research Achievements

Do mice with specific behavioral features of depression share the same neural substrates as human patients? By comparing pre-depression and depression-like states using calcium imaging, we found that stress- and inflammation-induced depressed mice showed increased spontaneous neural activity in the infralimbic cortex (IL), the mouse equivalent of the brain area where patients show abnormalities, compared to other brain areas. This finding suggests that there is a potential for shared pathological mechanisms between humans and mice and supports the validity of using animal models to study depression.

Academic Significance and Societal Importance of the Research Achievements

あらゆる疾患モデルにおいて病態の生物学的基盤の再現は不可欠である。しかしながら、うつ病研究はモデル動物と患者に共通した生物学的基盤が存在しない状態で進められ、基礎と臨床を繋ぐ根幹が欠けた不完全な状態にある。本研究成果はうつ病患者とうつマウスの脳活動が同じ神経活動基盤を有しており、うつモデルマウスに神経活動に基づく構成的妥当性を付与できる可能性を示している。本研究の発展は社会生活を損なう疾患として世界的な問題となっているうつ病のトランスレーショナルリサーチを推進し、病態に基づいた診断、治療を開発する根拠となることが期待できる。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (6 results)

All 2023 2022 2020

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

  • [Journal Article] Association between vascular endothelial growth factor-mediated blood–brain barrier dysfunction and stress-induced depression2022

    • Author(s)
      Hitomi Matsuno, Shoko Tsuchimine, Kazunori O'Hashi, Kazuhisa Sakai, Kotaro Hattori, Shinsuke Hidese, Shingo Nakajima, Shuichi Chiba, Aya Yoshimura, Noriko Fukuzato, Mayumi Kando, Megumi Tatsumi Shintaro Ogawa, Noritaka Ichinohe, Hiroshi Kunugi, and Kazuhiro Sohya
    • Journal Title

      Molecular Psychiatry

      Volume: 27 Issue: 9 Pages: 3822

    • DOI

      10.1038/s41380-022-01618-3

    • URL

      https://localhost/en/publications/4d3f3f46-8826-4ca3-b086-9762600034ba

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Repetitive nociceptive stimulation increases spontaneous neural activation similar to nociception-induced activity in mouse insular cortex2022

    • Author(s)
      Kobayashi Shutaro、O’Hashi Kazunori、Kobayashi Masayuki
    • Journal Title

      Scientific Reports

      Volume: 12 Issue: 1 Pages: 1-9

    • DOI

      10.1038/s41598-022-19562-1

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A new phenotype identification method with the fluorescent expression in cross-sectioned tails in <i>Thy1</i>-GCaMP6s transgenic mice2022

    • Author(s)
      Kobayashi Shutaro、O’Hashi Kazunori、Kaneko Keisuke、Kobayashi Satomi、Ogisawa Shouhei、Tonogi Morio、Fujita Satoshi、Kobayashi Masayuki
    • Journal Title

      Journal of Oral Science

      Volume: 64 Issue: 2 Pages: 156-160

    • DOI

      10.2334/josnusd.21-0528

    • NAID

      130008160484

    • ISSN
      1343-4934, 1880-4926
    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Cortical representation for orofacial noxious information in mouse2023

    • Author(s)
      O'Hashi K, Kobayashi M
    • Organizer
      第100回日本生理学会
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The spatial profile of orofacial nociceptive information foci in mouse insular cortex2022

    • Author(s)
      O'Hashi K, Kobayashi S, Kobayashi M
    • Organizer
      44th Annual Meeting of the Japan Neuroscience Society
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Neural homology of major depressive disorder between human and mouse2020

    • Author(s)
      Kazunori Ohashi, Kazuhiro Sohya, Hitomi Matsuno, Shoko Tsuchimine, Hiroshi Kunugi
    • Organizer
      The 43rd Annual Meeting of the Japan Neuroscience Society
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research

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Published: 2020-04-28   Modified: 2024-01-30  

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