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Expression of neurotrypsin in dorsal root ganglia and dorsal horn following peripheral nerve injury

Research Project

Project/Area Number 17K09047
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pain science
Research InstitutionHyogo Medical University

Principal Investigator

Hiroki Yamanaka  兵庫医科大学, 医学部, 講師 (20340995)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsセリンプロテアーゼ / 細胞外環境改変 / シナプス可塑性 / 脊髄後角 / 後根神経節 / 神経傷害性疼痛 / ニューロトリプシン / 痛み / 末梢神経損傷 / 痒み / 可塑性 / 後角ニューロン / 後角サーキット / 細胞外環境修飾 / 疼痛伝達 / ネットワーク / 細胞外基質蛋白 / タンパク分解 / ニューロン / シナプス / 細胞外プロテアーゼ
Outline of Final Research Achievements

It has been reported that Neurotrypsin (NP) plays an important role in the formation of neuromuscular junction and in the synaptic plasticity in nervous system. In this study we elucidated the expression of NP mRNA in the rat dorsal root ganglia (DRG) and dorsal horn (DH). In the rat DRG, 30% of total neuron expressed NP mRNA. And in DH, neuronal cell in laminae I-II expressed NP mRNA but not in deep layer of DH. Peripheral nerve injury dramatically increased the NP mRNA expression in DRG but not in DH. Agrin is specific substrate of NP and the fragment of agrin act as a specific ligand of cell surface tyrosin kinase Muscle specific kinase (MuSK). We found the phosphorylation of MuSK in the activated microglia of the neuropathic pain model rats. These results indicate the possible involvement of NP in neuro-microglia interaction following peripheral nerve injury.

Academic Significance and Societal Importance of the Research Achievements

本研究課題は痛覚伝導路において細胞外環境を改変し、シナプス可塑性に関わるニューロトリプシンの特異的な発現を明らかにできる。痛覚過敏を主症状とする神経傷害性疼痛が難治性であるメカニズムの1つが神経回路網の形態的な変化である。このため、形態変化を可能にする細胞外環境改変因子は難治性疼痛に対しての責任分子の1つである事が考えられる。従って痛覚伝導路の特異的に発現し、損傷応答して発現増加をしめしているニューロトリプシンは、神経傷害性疼痛をはじめとした疼痛の治療ターゲット分子となる可能性が高いと考えられる。今後は特異的な活性阻害剤の開発が今後の課題であると思われる。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (5 results)

All 2020 2019

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

  • [Journal Article] Hippocalcin-like 4, a neural calcium sensor, has a limited contribution to pain and itch processing2020

    • Author(s)
      Christopher G. Alvaro, Joao M. Braz, Mollie Bernstein, Katherine A. Hamel,Veronica Craik, Hiroki Yamanaka, Allan I. Basbaum.
    • Journal Title

      PLoS One

      Volume: 15 Issue: 2 Pages: e0226289-e0226289

    • DOI

      10.1371/journal.pone.0226289

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Differential expression of mGluRs in rat spinal dorsal horns and their modulatory effects on nocifensive behaviors2019

    • Author(s)
      Okubo Masamichi、Yamanaka Hiroki、Kobayashi Kimiko、Noguchi Koichi
    • Journal Title

      Molecular Pain

      Volume: 15 Pages: 1-13

    • DOI

      10.1177/1744806919875026

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] TRPA1-expressing lamina propria mesenchymal cells regulate colonic motility through prostaglandin release2019

    • Author(s)
      Yang Yanjing, Wang Shenglan, Kobayashi Kimiko, Kanda Hirosato, Kogure Yoko, Yamamoto Satoshi, Yamanaka Hiroki, Noguchi Koichi, Dai Yi .
    • Organizer
      The 49th Annual Meeting of the Society for Neuroscience
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 脊髄後角神経回路におけるmGluRの発現解析と炎症性疼痛との関係2019

    • Author(s)
      大久保 正道, 山中 博樹, 小林 希実子,野口 光一
    • Organizer
      第124回日本解剖学会総会・全国学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 末梢神経損傷後の脊髄後角neuronで増加するBDNF2019

    • Author(s)
      小林 希実子, 山中 博樹, 大久保 正道, 野口光一
    • Organizer
      第124回日本解剖学会総会・全国学術集会
    • Related Report
      2019 Annual Research Report

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Published: 2017-04-28   Modified: 2021-02-19  

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