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The Mechanism of Mechanical Stress Response in Hippocampal Cells

Research Project

Project/Area Number 21K11330
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 InstitutionNational Rehabilitation Center for Persons with Disabilities

Principal Investigator

Maekawa Takahiro  国立障害者リハビリテーションセンター(研究所), 研究所 運動機能系障害研究部, 研究員 (50782471)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2023: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2022: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Keywords力学的刺激(メカニカルストレス) / 海馬 / 抗炎症 / 認知機能 / 力学的刺激 / メカニカルストレス / 流体剪断力
Outline of Research at the Start

運動は脳内の記憶を司る海馬での神経新生を誘導し、認知機能を向上させることが分かっている。運動による認知機能改善のメカニズムを、運動時に身体局所に加わる、あるいは生じる力学的刺激(メカニカルストレス)という観点から解析する。本研究では、メカニカルストレスを受容し生物学的信号に変換するメカニズム、すなわちメカノセンサーを明らかにすべく、メカニカルストレスに対する海馬の細胞応答を調べ、認知機能改善・向上効果が最大となるメカニカルストレスを探索し、認知症予防や治療への応用を図る。

Outline of Final Research Achievements

The aim of this study is to investigate whether passive mechanical stress affects cellular responses in the hippocampus by considering exercise as mechanical stimulation (mechanical stress) on tissues and cells. By gelling the interstitial fluid in the hippocampus of mice using polyethylene glycol (PEG) solution, it was found that cognitive function declined, suggesting that activity-dependent interstitial fluid flow may maintain cellular homeostasis in the hippocampus. However, when passive mechanical stress was applied to the heads of senescence-accelerated model mice, instead of showing anti-inflammatory and cognitive improvement effects, the results showed increased inflammation and a decline in cognitive function, contrary to our hypothesis.

Academic Significance and Societal Importance of the Research Achievements

運動による抗炎症、認知機能維持・改善の機構として体内での代謝的変動などが中心的に研究されており、脳内において運動刺激をメカニカルストレスとして捉えた研究はない。本研究では麻酔下で老化促進モデルマウスの頭部に受動的なメカニカルストレスを加えると炎症反応の促進および認知機能を低下させる結果となったが、脳内が直接的なメカニカルストレスに反応することを確認することができた。別の脳疾患モデルやメカニカルストレスの大きさを変化させ、抗炎症、認知機能維持・改善効果を持つ条件を検証し、高齢者や運動器障害者の認知機能維持・改善を目的とした運動療法や機器開発への応用を目指す。

Report

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

    (4 results)

All 2023 2022 2021

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

  • [Journal Article] Interstitial-fluid shear stresses induced by vertically oscillating head motion lower blood pressure in hypertensive rats and humans2023

    • Author(s)
      Murase Shuhei、Sakitani Naoyoshi、Maekawa Takahiro、Yoshino Daisuke、Takano Kouji、Konno Ayumu、Hirai Hirokazu、Saito Taku、et al
    • Journal Title

      Nature Biomedical Engineering

      Volume: 7 Issue: 11 Pages: 1350-1373

    • DOI

      10.1038/s41551-023-01061-x

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Application of Passive Head Motion to Generate Defined Accelerations at the Heads of Rodents2022

    • Author(s)
      Maekawa Takahiro、Sakitani Naoyoshi、Ryu Youngjae、Takashima Atsushi、Murase Shuhei、Fink Julius、Nagao Motoshi、Ogata Toru、Shinohara Masahiro、Sawada Yasuhiro
    • Journal Title

      Journal of Visualized Experiments

      Volume: - Issue: 185 Pages: 363100-363100

    • DOI

      10.3791/63100

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Human chorionic gonadotropin treatment: a viable option for management of secondary hypogonadism and male infertility.2021

    • Author(s)
      Julius Fink, Brad J. Schoenfeld, Anthony C. Hackney, Takahiro Maekawae & Shigeo Horie
    • Journal Title

      Expert Review of Endocrinology & Metabolism

      Volume: 16 Issue: 1 Pages: 1-8

    • DOI

      10.1080/17446651.2021.1863783

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Book] 実験医学増刊 Vol.40 No.2 健康寿命の鍵を握る骨格筋2022

    • Author(s)
      﨑谷直義, 前川貴郊, 澤田泰宏
    • Total Pages
      227
    • Publisher
      羊土社
    • ISBN
      9784758104005
    • Related Report
      2021 Research-status Report

URL: 

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

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