Identification of thermosensitive molecules involved in microglia movement

• Project/Area Number: 17K16731
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Anesthesiology
• Research Institution: Okayama University
• Principal Investigator: Nishimoto Rei 岡山大学, 医学部, 客員研究員 (60789585)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: ミクログリア / イオンチャネル / 温度感受性 / 低体温療法

Outline of Final Research Achievements

Microglia maintain central nervous system homeostasis by monitoring changes in their environment. Microglial dysfunction including abnormality in microglia movement could cause neural network failure. In this study, we found that mouse microglia exhibit temperature-dependent movement in vitro and in vivo that is mediated by TRPV4 channels within the physiological range of body temperature. Our findings may provide a new basis for future research into the potential clinical application of temperature regulation to preserve cell function via manipulation of ion channel activity.

Academic Significance and Societal Importance of the Research Achievements

温度を感じるイオンチャネルが存在することの生理学的意義について、未だ全てが解明されてはいない。この研究では、中枢神経系の恒常性を担うミクログリアという細胞は、温度感受性イオンチャネルTRPV4を介して温度を感じて動きを変化させることを明らかにした。すなわち、ミクログリア細胞の機能維持には温度感受性イオンチャネルTRPV4が必要であることがわかった。ミクログリアは神経活動を制御することから、ミクログリアの機能保持とそれによる神経保護を目的とした創薬分野の開拓に寄与できる可能性がある。

Research Products

• [Journal Article] Thermosensitive TRPV4 channels mediate temperature-dependent microglia movement (2021)
  • Author(s): Rei Nishimoto, Sandra Derouiche, Kei Eto, Aykut Deveci, Makiko Kashio, Yoshitaka Kimori, Yoshikazu Matsuoka, Hiroshi Morimatsu, Junichi Nabekura, and Makoto Tominaga
  • Journal Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 118 Issue: 17
  • DOI: 10.1073/pnas.2012894118
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Microglia Movement is Temperature-dependent (2019)
  • Author(s): Rei Nishimoto, Sandra Derouiche, Makiko Kashio, Yoshikazu Matsuoka, Hiroshi Morimatsu, Makoto Tominaga
  • Organizer: 2019 Annual Meeting of the American Society of Anesthesiologists
  • Int'l Joint Research
• [Presentation] Involvement of thermosensitive TRP channels in temperature-dependent microglia movement (2019)
  • Author(s): Sandra Derouiche, Rei Nishimoto, Kei Eto, Makoto Tominaga
  • Organizer: 9th of Federation of the Asian and Oceanian Physiological Societies in conjunction with the 96th annual meeting of the Physiological Society of Japan
  • Int'l Joint Research
• [Presentation] Involvement of thermosensitive TRP channels in temperature-dependent microglia movement. (2018)
  • Author(s): デルーチ サンドラ、西本れい、富永真琴
  • Organizer: 第９５回日本生理学会大会
• [Presentation] ミクログリアの動きは温度依存的である (2017)
  • Author(s): 西本れい、デルーチ サンドラ、富永真琴
  • Organizer: 第６４回日本麻酔科学会学術集会
• [Remarks] 脳の免疫細胞ミクログリアが温度を感じて動くことを発見
  • URL: https://www.nips.ac.jp/release/2021/04/post_437.html
• [Remarks] 脳の免疫細胞ミクログリアが温度を感じて動くメカニズムを解明
  • URL: https://www.okayama-u.ac.jp/tp/release/release_id821.html