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Elucidation of extracellular molecular brain pathology related to stress-related affective disorder

Planned Research

Project AreaInnovative nanotechnology for probing molecular landscapes in the brain
Project/Area Number 21H05091
Research Category

Grant-in-Aid for Transformative Research Areas (B)

Allocation TypeSingle-year Grants
Review Section Transformative Research Areas, Section (II)
Research InstitutionNagoya University

Principal Investigator

Takemoto-Kimura Sayaka  名古屋大学, 環境医学研究所, 教授 (70372365)

Co-Investigator(Kenkyū-buntansha) 宮田 茂雄  日本薬科大学, 薬学部, 准教授 (40366836)
Project Period (FY) 2021-08-23 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥40,690,000 (Direct Cost: ¥31,300,000、Indirect Cost: ¥9,390,000)
Fiscal Year 2023: ¥13,520,000 (Direct Cost: ¥10,400,000、Indirect Cost: ¥3,120,000)
Fiscal Year 2022: ¥13,520,000 (Direct Cost: ¥10,400,000、Indirect Cost: ¥3,120,000)
Fiscal Year 2021: ¥13,650,000 (Direct Cost: ¥10,500,000、Indirect Cost: ¥3,150,000)
Keywordsストレス / 情動障害 / マイクロダイアリシス / イメージング / 分子病態 / 高分子ミセル / 脳内分子 / 情動変化 / 脳深部イメージング
Outline of Research at the Start

脳によって生起する情動(不安、恐怖、快楽など)は、生物が生存するうえで必要不可欠な生理機能である。現代社会における様々なストレスが一因となり、過度な情動の亢進や消失といった情動障害が生じ、うつ病や適応障害、不安障害をはじめとする精神疾患との病態に関与するとされる。本研究では、特に細胞外分子の変化を捉えるために、脳深部イメージング法やマイクロダイアリシス法などの分子脳生物学的手法を組み合わせ、ストレスに伴う情動障害の病態解明を目指し、モデルマウスを対象とした研究を推進する。

Outline of Final Research Achievements

Emotions generated by the brain (anxiety, fear, pleasure, etc.) are essential for the survival of animals. Various stresses in modern society are known to lead to some dysfunctions in emotional responses, which are considered to be involved in the pathophysiology of neuropsychiatric diseases such as depression, PTSD, and anxiety disorders. In this research, using animal models for emotional disorders, we conducted multifaced analysis,including behavioral and transcriptomic analysis. Furthermore, in order to specifically detect changes in extracellular molecules and find associated changes in neural activity, we developed and performed deep brain imaging and microdialysis were conducted to elucidate alterations in extracellular molecules. By these methods, we aimed to elucidate the molecular pathology of emotional disorders associated with stress.

Academic Significance and Societal Importance of the Research Achievements

本研究では、独自に開発した病態モデルを含めた様々な情動異常を示すモデルマウスを対象とし、多階層の病態解明を推進した。情動の変化は、様々な神経・精神疾患で認められ、患者本人や周囲にも多大な損失を与えるため、その病態解明は喫緊の課題である。本研究により病態モデルが開発されその研究基盤が整備されるとともに、病態の一端が解明された。

Report

(3 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Annual Research Report
  • Research Products

    (9 results)

All 2023 2022

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (6 results)

  • [Journal Article] Experience-dependent changes in affective valence of taste in male mice2023

    • Author(s)
      Hamada Shun、Mikami Kaori、Ueda Shuhei、Nagase Masashi、Nagashima Takashi、Yamamoto Mikiyasu、Bito Haruhiko、Takemoto-Kimura Sayaka、Ohtsuka Toshihisa、Watabe Ayako M.
    • Journal Title

      Molecular Brain

      Volume: 16 Issue: 1 Pages: 28-28

    • DOI

      10.1186/s13041-023-01017-x

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Forster resonance energy transfer-based kinase mutation phenotyping reveals an aberrant facilitation of Ca2+/calmodulin-dependent CaMKIIα activity in de novo mutations related to intellectual disability2022

    • Author(s)
      Fujii Hajime、Kidokoro Hiroyuki、Kondo Yayoi、Kawaguchi Masahiro、Horigane Shin-ichiro、Natsume Jun、Takemoto-Kimura Sayaka、Bito Haruhiko
    • Journal Title

      Frontiers in Molecular Neuroscience

      Volume: 15 Pages: 1-20

    • DOI

      10.3389/fnmol.2022.970031

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Glioma facilitates the epileptic and tumor-suppressive gene expressions in the surrounding region2022

    • Author(s)
      Komiyama Kazuki、Iijima Keiya、Kawabata-Iwakawa Reika、Fujihara Kazuyuki、Kakizaki Toshikazu、Yanagawa Yuchio、Yoshimoto Yuhei、Miyata Shigeo
    • Journal Title

      Scientific Reports

      Volume: 12 Issue: 1

    • DOI

      10.1038/s41598-022-10753-4

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 扁桃体微小神経核における情動および社会的行動制御の分子基盤探索2023

    • Author(s)
      竹本さやか, 上田修平
    • Organizer
      第96回日本生化学会大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 扁桃体微小神経核を介した情動制御分子基盤の解明2023

    • Author(s)
      竹本さやか, 上田修平
    • Organizer
      第46回日本分子生物学会年会
    • Related Report
      2023 Annual Research Report
  • [Presentation] こころの疾患“うつ病”のバイオマーカー探索~脳分子探査に期待すること~2023

    • Author(s)
      宮田茂雄
    • Organizer
      第96回日本生化学会大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 扁桃体微小神経核における情動制御分子基盤の探索2022

    • Author(s)
      竹本 さやか
    • Organizer
      第95回日本生化学会大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Exploring the molecular and neuronal bases involved in central amygdala-dependent control of emotional behaviors2022

    • Author(s)
      Takemoto-Kimura S, Ueda S
    • Organizer
      第96回日本薬理学会年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] ストレスにより変動するマウス脳内微量細胞外分子の網羅的探索2022

    • Author(s)
      宮田茂雄
    • Organizer
      第96回日本薬理学会年会
    • Related Report
      2022 Annual Research Report

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Published: 2021-10-22   Modified: 2025-01-30  

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