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Elucidation of the neural basis controlling anxiety through multi-scale analysis

Research Project

Project/Area Number 20H03391
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 47040:Pharmacology-related
Research InstitutionOsaka University

Principal Investigator

Kasai Atsushi  大阪大学, 大学院薬学研究科, 准教授 (40454649)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2022: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2021: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2020: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
Keywords不安 / イメージング / シングル細胞解析 / ストレス / 前障 / 全脳 / 全脳解析 / 不安障害 / うつ / RNAシークエンス
Outline of Research at the Start

近年、不安障害の患者数は急増しており、認知症患者数よりも多く、社会負担が甚大なが
ら、成因・病態機構や治療機序が未解明で新規治療薬の開発も長年失敗している。本研究では、それを打開するため、応募者らが最近開発した方法論を駆使し、従来研究では見逃されていた病態の詳細な分子・神経基盤の解明を通じ、新たな治療法の確立に貢献する。具体的には、最新の高精細全脳イメージング法および単一細胞トランスクリプトーム解析法を組み合わせ、強い精神的ストレスに暴露された脳を、全脳細胞レベルで解析し、ストレス誘発不安様行動を制御する神経基盤を明らかにする。

Outline of Final Research Achievements

In recent years, the number of patients with anxiety disorders has increased, imposing a significant social burden. Despite this, the causes, pathological mechanisms, and treatment mechanisms remain unclear. In this study, we combined the latest high-resolution whole-brain imaging technique and single-cell transcriptome analysis methods to analyze the brain exposed to severe mental stress at the single cell level, revealing new neural bases that control stress-induced anxiety-related behaviors. Specifically, we clarified the neural circuit structure and cellular characteristics of stress-responsive neurons in the claustrum. These results suggest that the molecular characteristics in the claustrum could lead to the identification of new therapeutic targets for anxiety-related disorders.

Academic Significance and Societal Importance of the Research Achievements

不安症やうつ病の新規治療薬の第一選択薬は、選択的セロトニン再取り込み阻害薬であり、過去数十年間新薬は出ていない。しかし、うつ病患者の約3割は、既存の抗うつ薬では治療効果が得られない難治性であるとされている。そのため、新たな機序の抗うつ薬・不安症等の治療薬開発が求められている。本研究によって同定されたストレス応答性の細胞集団は、これらストレス性精神疾患の新たな標的になることが期待される。

Report

(4 results)
  • 2023 Final Research Report ( PDF )
  • 2022 Annual Research Report
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • Research Products

    (8 results)

All 2023 2022 2021

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

  • [Journal Article] Acute social defeat stress activated neurons project to the claustrum and basolateral amygdala2022

    • Author(s)
      Tanuma Masato、Niu Misaki、Ohkubo Jin、Ueno Hiroki、Nakai Yuka、Yokoyama Yoshihisa、Seiriki Kaoru、Hashimoto Hitoshi、Kasai Atsushi
    • Journal Title

      Molecular Brain

      Volume: 15 Issue: 1 Pages: 100-100

    • DOI

      10.1186/s13041-022-00987-8

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Claustrum mediates bidirectional and reversible control of stress-induced anxiety responses.2022

    • Author(s)
      Niu M, Kasai A, Tanuma M, Seiriki K, Igarashi H, Kuwaki T, Nagayasu K, Miyaji K, Ueno H, Tanabe W, Seo K, Yokoyama R, Ohkubo J, Ago Y, Hayashida M, Inoue KI, Takada M, Yamaguchi S, Nakazawa T, Kaneko S, Okuno H, Yamanaka A, Hashimoto H.
    • Journal Title

      Science Advances

      Volume: 8 Issue: 11

    • DOI

      10.1126/sciadv.abi6375

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Altered Functional Connectivity of the Orbital Cortex and Striatum Associated with Catalepsy Induced by Dopamine D1 and D2 Antagonists2021

    • Author(s)
      Misaki Niu, Atsushi Kasai, Kaoru Seiriki, Misuzu Hayashida, Masato Tanuma, Rei Yokoyama, Yumi Hirato, Hitoshi Hashimoto
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 44 Issue: 3 Pages: 442-447

    • DOI

      10.1248/bpb.b20-01006

    • NAID

      130007993460

    • ISSN
      0918-6158, 1347-5215
    • Year and Date
      2021-03-01
    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Comprehensive brain-wide analysis of disease model mice toward elucidating the pathology of mental disorder2023

    • Author(s)
      Atsushi Kasai, Hitoshi Hashimoto
    • Organizer
      The 46th Annual meeting of the Japan Neuroscience Society
    • Related Report
      2022 Annual Research Report
  • [Presentation] Claustrum mediates stress-induced anxiety responses and stress resistance2022

    • Author(s)
      Atsushi Kasai, Misaki Niu, Masato Tanuma, Kaoru Seiriki, Hitoshi Hashimoto
    • Organizer
      Cell Symposia
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The mechanisms of stress-induced anxiety responses revealed by brain-wide neuronal activation mapping2022

    • Author(s)
      Atsushi Kasai
    • Organizer
      Neuro2022
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 全脳イメージングシステムFASTの開発と精神・神経疾患研究への応用2022

    • Author(s)
      笠井淳司
    • Organizer
      生体機能と創薬シンポジウム2022
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Monitoring neuronal activation at the local and global levels provides a new role of claustral neurons in the neuronal mechanisms of anxiety-related behaviors2021

    • Author(s)
      Atsushi Kasai et al
    • Organizer
      第64回日本薬理学会年会
    • Related Report
      2020 Annual Research Report

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Published: 2020-04-28   Modified: 2025-01-30  

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