Molecular mechanisms of peripheral nerve regeneration by rehabilitation

2020 Fiscal Year Final Research Report

• Project/Area Number: 18H03124
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 59010:Rehabilitation science-related
• Research Institution: University of Nagasaki (2020); Gunma University (2018-2019)
• Principal Investigator: Shibasaki Koji 長崎県立大学, 看護栄養学部, 教授 (20399554)
• Co-Investigator(Kenkyū-buntansha): 岡部 弘基 東京大学, 大学院薬学系研究科(薬学部), 助教 (20455398)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: TRPV2 / メカノセンサー / 神経再生 / リハビリ / 機械刺激

Outline of Final Research Achievements

The passive stretching-dependent axonal outgrowth occurs in our body. It has never been identified for a long time which molecules are the mechanosensors for it. We previously reported that TRPV2 was a mechanosensor channel which contributed axonal outgrowth in membrane stretch dependent manner. These results indicate that TRPV2 might be an important component for passive stretching, if TRPV2 can detect very weak mechanical stimulus. In this study, we examined whether TRPV2 can detect such very weak mechanical stimulus by a Ca2+-imaging method and a whole-cell patch clamp recording. We also examined whether the activation of TRPV2 by weak mechanical stimulus lead to the enhancement of axonal outgrowth by rehabilitation. Finally, we identified that TRPV2 had a potential to detect very weak mechanical stimulus, and the activation of TRPV2 can regenerate damaged axons.

Free Research Field

分子神経生理学

Academic Significance and Societal Importance of the Research Achievements

申請者が作製した感覚神経特異的なTRPV2KOマウス（TRPV2CKOマウス）を用いて、損傷神経の再生能を比較したところ、野生型（WT）マウスと比較して、TRPV2CKOでは軸索再生が著しく減弱することを見いだした。また、どうして軸索再生能が減弱するのか、その分子基盤を明らかにした。
これらの結果から、末梢神経の再生に対するリハビリやマッサージの効果に対して、TRPV2のメカノセンサー機能を指標に科学的に分子機構を述べることが可能になった。この成果を応用することでより効果的なリハビリ手法の開発へとつながる。