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Experimental research on regenerative treatment of axon and muscle fiber for nerve and muscle dysfunction by methylmercury

Research Project

Project/Area Number 19K07077
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
Research InstitutionNational Institute for Minamata Disease

Principal Investigator

Fujimura Masatake  国立水俣病総合研究センター, その他部局等, 部長 (20416564)

Co-Investigator(Kenkyū-buntansha) 中村 篤  国立水俣病総合研究センター, その他部局等, 医療系職員 (40785713)
臼杵 扶佐子  鹿児島大学, ヒトレトロウイルス学共同研究センター, 客員研究員 (50185013)
Project Period (FY) 2019-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsメチル水銀 / 神経機能障害 / 筋機能障害 / 神経障害性疼痛 / ROCK阻害剤 / 振動刺激処置 / 神経軸索 / 筋線維 / 振動刺激
Outline of Research at the Start

未だ解決されていないメチル水銀による神経機能障害の根本治療を可能にするために、神経軸索の再生メカニズムに着目したROCK阻害剤による薬物治療の可能性について実験的に明らかにし、臨床研究へ繋げる (基礎研究から臨床研究へのアプローチ)。さらに、神経機能障害に伴う筋機能障害については、これまで臨床研究によって振動刺激が有効であることが示されているが、そのメカニズムについては十分に解明されていないことから、実験動物を用いて振動刺激の筋機能障害に対する作用メカニズムを理論的に明らかにし、臨床研究へ還元する (臨床研究から基礎研究へのアプローチ)。

Outline of Final Research Achievements

Research conducted up to FY2028 revealed that ROCK inhibitors and vibration stimulation were effective in the treatment of neurofunctional disorders and muscle dysfunction, which was the initial goal of the project. Then, research on neuropathic pain caused by methylmercury exposure was initiated in FY2021. In FY2021, we succeeded in creating a neuropathic pain model induced by methylmercury, and in FY2022, we used this model to demonstrate that the ROCK inhibitor Fasudil suppressed neuropathic pain. Furthermore, in FY2023, we demonstrated that gabapentin (which is clinically used for general neuropathic pain) suppressed neuropathic pain in this model.

Academic Significance and Societal Importance of the Research Achievements

本研究成果の学術的意義や社会的意義目的は、水俣病を代表とするメチル水銀中毒において引き起こされる神経機能障害および筋機能障害の治療を可能にするために、メチル水銀中毒動物モデルを用いてその発症メカニズムを実験的に明らかにし、さらにその発症メカニズムに基づいた薬剤等による治療効果を実験的に明らかにすることによってメチル水銀中毒の治療についての有益な情報を得ることである。

Report

(6 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (14 results)

All 2023 2022 2021 2020 2019 Other

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 2 results) Presentation (6 results) (of which Int'l Joint Research: 2 results) Book (1 results) Remarks (2 results)

  • [Journal Article] Fasudil, a ROCK inhibitor, prevents neuropathic pain in Minamata disease model rats.2022

    • Author(s)
      Fujimura M
    • Journal Title

      Toxicol. Lett.

      Volume: 371 Pages: 38-45

    • DOI

      10.1016/j.toxlet.2022.10.001

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Cellular conditions responsible for methylmercury-mediated neurotoxicity.2022

    • Author(s)
      Fujimura M, Usuki F
    • Journal Title

      Int. J. Mol. Sci.

      Volume: 23 Issue: 13 Pages: 7218-7218

    • DOI

      10.3390/ijms23137218

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Methylmercury induces hyperalgesia/allodynia through spinal cord dorsal horn neuronal activation and subsequent somatosensory cortical circuit formation in rats2021

    • Author(s)
      Fujimura M, Usuki F, Nakamura A
    • Journal Title

      Archives of Toxicology

      Volume: 95 Issue: 6 Pages: 2151-2162

    • DOI

      10.1007/s00204-021-03047-7

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Local Vibration Stimuli Induce Mechanical Stress-Induced Factors and Facilitate Recovery From Immobilization-Induced Oxidative Myofiber Atrophy in Rats2019

    • Author(s)
      Usuki F, Fujimura M, Nakamura A, Nakano J, Okita M, Higuchi I
    • Journal Title

      Front Physiol

      Volume: 10 Pages: 759-759

    • DOI

      10.3389/fphys.2019.00759

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Fasudil, a Rho-Associated Coiled Coil-Forming Protein Kinase Inhibitor, Recovers Methylmercury-Induced Axonal Degeneration by Changing Microglial Phenotype in Rats2019

    • Author(s)
      Fujimura M, Usuki F, Nakamura A
    • Journal Title

      Toxicol Sci

      Volume: 168 Issue: 1 Pages: 126-136

    • DOI

      10.1093/toxsci/kfy281

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Presentation] メチル水銀曝露はラット足底部に末梢および中枢神経傷害を介した神経障害性疼痛を引き起こす2023

    • Author(s)
      藤村成剛
    • Organizer
      第50回日本毒性学会
    • Related Report
      2023 Annual Research Report
  • [Presentation] メチル水銀曝露ラットに生じる疼痛閾値低下に対する各種薬剤の効果2023

    • Author(s)
      藤村成剛, 臼杵扶佐子, 中村篤
    • Organizer
      令和5年度メチル水銀研究ミーティング
    • Related Report
      2023 Annual Research Report
  • [Presentation] Methylmercury induces allodynia through activation of inflammatory microglia in spinal cord and subsequent stimulation in somatosensory cortex od rats2021

    • Author(s)
      Fujimura M, Usuki F, Nakamura A
    • Organizer
      60th Annual Meeting, Society of Toxicology
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] メチル水銀曝露はラット足底部に神経障害性疼痛の1種である疼痛閾値低下 (アロディニア) を引き起こす2020

    • Author(s)
      藤村成剛, 臼杵扶佐子, 中村篤
    • Organizer
      メタルバイオサイエンス研究会2020
    • Related Report
      2020 Research-status Report
  • [Presentation] Fasudil, a ROCK inhibitor, recovers methylmercury-induced axonal degeneration by changing microglial phenotype in rats2019

    • Author(s)
      Fujimura M, Usuki F, Nakamura A
    • Organizer
      14th International Conference on Mercury as a Global Pollutant
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 局所振動刺激はラットにおいてメカノストレス因子を誘導し不動化による筋萎縮からの回復を促進する2019

    • Author(s)
      藤村成剛, 臼杵扶佐子, 中村篤, 中野治郎, 沖田実, 樋口逸郎
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Research-status Report
  • [Book] Handbook of Neurotoxicity2021

    • Author(s)
      Fujimura M, Usuki F
    • Total Pages
      16
    • Publisher
      Springer, Cham
    • ISBN
      9783030715199
    • Related Report
      2021 Research-status Report
  • [Remarks] 国立水俣病総合研究センターホームページ→藤村成剛

    • URL

      http://nimd.env.go.jp/about/organization/member04.html

    • Related Report
      2023 Annual Research Report 2022 Research-status Report
  • [Remarks] 国立水俣病総合研究センター/ 職員紹介/ 藤村成剛

    • URL

      http://nimd.env.go.jp/kakubu/kiso/fujimura.html

    • Related Report
      2019 Research-status Report

URL: 

Published: 2019-04-18   Modified: 2025-01-30  

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