Regulation of neuroplasticity after spinal cord injury via mechanosensor Cas-dependent regulation of microglial activity

• Project/Area Number: 16K16457
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Rehabilitation science/Welfare engineering
• Research Institution: Tottori University (2017-2018); The University of Tokyo (2016)
• Principal Investigator: ICHIHARA Yoshinori 鳥取大学, 医学部, 助教 (50710711)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); 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); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: ミクログリア / マクロファージ / メカニカルストレス / シアストレス / 脊髄損傷

Outline of Final Research Achievements

The microglia activity is important for neuronal plasticity, which relates to the recovery of neural function after rehabilitation. The contribution of mechanical stresses to the microglial activity in the injured spinal cord was investigated by in vitro and in vivo experiments. I clarified that macrophages, in which microglia is categorized, have the ability to respond to mechanical stress and differently respond to each kind of mechanical stresses. Moreover, the microglia around the scar area might receive mechanical stress differently to another area. These findings might indicate the contribution of mechanical stress to microglial activity in the injured spinal cord.

Academic Significance and Societal Importance of the Research Achievements

本研究により、ミクログリアと同系統の細胞であるマクロファージがメカニカルストレスに反応すること、損傷脊髄でミクログリアが部位ごとに多様なメカニカルストレスを受けている可能性が示唆された。これは、損傷脊髄でのメカニカルストレスの役割を解明する一助となるものであり、将来のメカニカルストレス制御を標的としたリハビリテーション法の確立の基盤となることや、リハビリ効果の分子メカニズムの解明につながるものである。

Research Products

• [Journal Article] Local cyclical compression modulates macrophage function in situ and alleviates immobilization-induced muscle atrophy (2018)
  • Author(s): 1.Saitou K, Tokunaga M, Yoshino D, Sakitani N, Maekawa T, Ryu Y, Nagao M, Nakamoto H, Saito T, Kawanishi N, Suzuki K, Ogata T, Makuuchi M, Takashima A, Sawada K, Kawamura S, Nakazato K, Kouzaki K, Harada I, Ichihara Y, Sawada Y
  • Journal Title: Clinical Science Volume: 132 Issue: 19 Pages: 2147-2161
  • DOI: 10.1042/cs20180432
  • NAID: 40021950316
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The swimming test is effective for evaluating spasticity after contusive spinal cord injury (2017)
  • Author(s): Ryu Y, Ogata T, Nagao M, Kitamura T, Morioka K, Ichihara Y, Doi T, Sawada Y, Akai M, Nishimura R, Fujita N
  • Journal Title: PLoS One Volume: 12 Issue: 2 Pages: e0171937-e0171937
  • DOI: 10.1371/journal.pone.0171937
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Copper chelater cuprizone inhibited high-fat diet induced adiposity. (2019)
  • Author(s): 市原克則、澤野達哉、楊潔、三明淳一朗、今村武史
  • Organizer: 第92回日本薬理学会年会