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Investigation of the spinal nerve regeneration using PAC

Research Project

Project/Area Number 19K09595
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56020:Orthopedics-related
Research InstitutionHamamatsu University School of Medicine

Principal Investigator

Matsuyama Yukihiro  浜松医科大学, 医学部, 教授 (20312316)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
KeywordsPAC / nerve regeneration / central nervous system / 脊髄損傷 / 脊髄再生 / カニクイザル
Outline of Research at the Start

光活性化アデニル酸シクラーゼ(Photoactivated Adenylyl Cyclase: PAC)はミドリムシの光応答から発見されたもので, 光刺激により生体でのcAMPの産生をコントロールできる分子である. 浜松ホトニクス社はこのPAC遺伝子をウィルスベクターを用いて細胞内に発現させ, 光刺激によって細胞内cAMP濃度を高精度に調整することを可能にした. そこで今回の目的はPACを用いた脊髄再生を評価することとする. マイクロインジェクション法を用いてラット脊髄にPACを導入し、機能回復をコントロールと比較する.その後はカニクイザルで同様の検討をおこなう.

Outline of Final Research Achievements

Photoactivated Adenylyl Cyclase (PAC) genetic vector was difficult to introduce in the spinal cord. Then, nerve regeneration ability of PAC vector was evaluated using optic nerves as a central nervous system. When a PAC -containing vector was introduced, the axon regeneration was confirmed from the damage site of nerve compared to the control vector. It was also confirmed that the function of the regenerative axis was restricted in a PAC -containing vector in which blue light irradiation was not performed. When comparing the PAC -containing vector and the damage model using the control vector, PAC -containing vector increased axon regeneration and number of axons significantly than the control vector.

Academic Significance and Societal Importance of the Research Achievements

中枢神経の再生において細胞内のcAMPが主要な役割を担っているという報告がある。今回、光活性化アデニル酸シクラーゼ(Photoactivated Adenylyl Cyclase: PAC)という光刺激により生体でのcAMPの産生をコントロールできる新技術を用いて中枢神経再生効果を組織レベルで評価した。マウスの中枢神経である視神経においてPAC導入により有意に神経再生効果がみられたことは学術的に新規性がある。また中枢神経再生は臨床的にはもちろんのこと、実験レベルにおいても困難な現状があるため、その再生をin vivoにて確認できたことは社会的意義も大きいと考える。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (1 results)

All 2019

All Journal Article (1 results) (of which Peer Reviewed: 1 results)

  • [Journal Article] Brain Activation in a Cynomolgus Macaque Model of Chymopapain-Induced Discogenic Low Back Pain: A Preliminary Study2019

    • Author(s)
      Hiroki Ushirozako, Go Yoshida, Daisuke Togawa, Takao Omura, Tomohiko Hasegawa, Yu Yamato, Tomohiro Banno, Hideyuki Arima, Shin Oe, Yuki Mihara, Tomohiro Yamada, Takahiro Natsume, Shinya Ogawa, Yuji Awaga, Hiroyuki Takamatsu, Yukihiro Matsuyama
    • Journal Title

      Spine Surgery and Related Research

      Volume: 3 Issue: 4 Pages: 368-376

    • DOI

      10.22603/ssrr.2018-0110

    • NAID

      130007734390

    • ISSN
      2432-261X
    • Year and Date
      2019-10-27
    • Related Report
      2019 Research-status Report
    • Peer Reviewed

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Published: 2019-04-18   Modified: 2023-01-30  

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