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Study of the effects of spontaneous and forced exercise on cognitive brain function in an animal model of Alzheimer's disease.

Research Project

Project/Area Number 21K11251
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 59010:Rehabilitation science-related
Research InstitutionKanazawa Medical University

Principal Investigator

YAMAKI Sachiko  金沢医科大学, 医学部, 特定助手 (70837715)

Co-Investigator(Kenkyū-buntansha) 加藤 伸郎  金沢医科大学, 医学部, 教授 (10152729)
小野 宗範  金沢医科大学, 医学部, 教授 (30422942)
伊藤 哲史  富山大学, 学術研究部医学系, 教授 (90334812)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2023: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsアルツハイマー病 / モデル動物 / 運動 / アミロイドβ / アミロイド前駆体 / 行動実験 / 組織学的解析
Outline of Research at the Start

超高齢化社会を迎えた現在、アルツハイマー病(AD)による認知症は大きな社会問題となっている。認知症の進行は身体的な機能低下と深く関わり、運動による身体能力向上は認知症の非薬物介入の中で重要な役割を占める。ただし、脳機能への影響という観点からは、AD認知症の神経活動障害および、運動が脳機能に及ぼす影響については不明な点が多い。この現状を踏まえ運動の認知機能に与える影響をADモデルマウスである3xTg-ADマウスを用いて検証する。特に意欲に基づく自発運動、および強制による運動それぞれが神経回路と学習行動に与える影響を精査し、認知症の運動療法の最適化への指針を確立することを目指す。

Outline of Final Research Achievements

Spatiotemporal changes in amyloid-β accumulation and tau phosphorylation in the 3xTg-AD mouse brain were auqntitatively examined and their patterns were determined. With these data, we were able to establish the pattern of pathological changes in the brain of 3xTg-AD mice and to determine the effects of exercise on the pathological changes. Based on these results, we tested the effects of 2 weeks of exercise on female 3xTg-AD mice, in which pathological changes are more pronounced, and found that 2 weeks of exercise could not produce improvements in cognitive function and pathological changes.

Academic Significance and Societal Importance of the Research Achievements

本研究の結果により明らかになった3xTg-ADマウス脳内の基本的な病理学的変化についての知見はこの動物を用いてのアルツハイマー病(AD)に対する様々な新規治療法を検証する際の基盤となる。3xTg-ADマウスは現時点においても神経原線維変化を生じる唯一のADモデルマウスであり有用である。また本研究から短期間の運動は、ADの病理変化に影響をもたらさないことが明らかとなった。このことから、さらに長期間の運動がADの改善には必要であることが示唆されたことは有効な運動療法の確立に向けての重要な知見であると考える。

Report

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

    (5 results)

All 2024 2022 2021 2020

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

  • [Journal Article] Spatiotemporal development of the neuronal accumulation of amyloid precursor protein and the amyloid plaque formation in the brain of 3xTg-AD mice2024

    • Author(s)
      Ono Munenori、Ito Tetsufumi、Yamaki Sachiko、Hori Yoshie、Zhou Qing、Zhao Xirun、Muramoto Shinji、Yamamoto Ryo、Furuyama Takafumi、Sakata-Haga Hiromi、Hatta Toshihisa、Hamaguchi Tsuyoshi、Kato Nobuo
    • Journal Title

      Heliyon

      Volume: 10 Issue: 7 Pages: e28821-e28821

    • DOI

      10.1016/j.heliyon.2024.e28821

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Disruption of sphingomyelin synthase 2 gene alleviates cognitive impairment in a mouse model of Alzheimer’s disease2024

    • Author(s)
      Uchiumi Osamu、Zou Jingyu、Yamaki Sachiko、Hori Yoshie、Ono Munenori、Yamamoto Ryo、Kato Nobuo
    • Journal Title

      Brain Research

      Volume: 1835 Pages: 148934-148934

    • DOI

      10.1016/j.brainres.2024.148934

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Vocalization during agonistic encounter in Mongolian gerbils: Impact of sexual experience2022

    • Author(s)
      Furuyama Takafumi、Shigeyama Takafumi、Ono Munenori、Yamaki Sachiko、Kobayasi Kohta I.、Kato Nobuo、Yamamoto Ryo
    • Journal Title

      PLOS ONE

      Volume: 17 Issue: 8 Pages: 1-17

    • DOI

      10.1371/journal.pone.0272402

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Amyloid β and Amyloid Precursor Protein Synergistically Suppress Large-Conductance Calcium-Activated Potassium Channel in Cortical Neurons.2021

    • Author(s)
      Yamamoto K, Yamamoto R, Kato N.
    • Journal Title

      Front Aging Neurosci.

      Volume: 13 Pages: 660319-660319

    • DOI

      10.3389/fnagi.2021.660319

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Remodeling of projections from ventral hippocampus to prefrontal cortex in Alzheimer's mice2020

    • Author(s)
      Xu Feng、Ono Munenori、Ito Tetsufumi、Uchiumi Osamu、Wang Furong、Zhang Yu、Sun Peng、Zhang Qing、Yamaki Sachiko、Yamamoto Ryo、Kato Nobuo
    • Journal Title

      Journal of Comparative Neurology

      Volume: 529 Issue: 7 Pages: 1486-1498

    • DOI

      10.1002/cne.25032

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research

URL: 

Published: 2021-04-28   Modified: 2025-01-30  

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