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Analysis of action of neurotrophic factor precursor via glutamatergic signal transmission that is involved in voiding dysfunction after spinal cord injury

Research Project

Project/Area Number 20K09575
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56030:Urology-related
Research InstitutionUniversity of Yamanashi

Principal Investigator

YOSHIYAMA Mitsuharu  山梨大学, 大学院総合研究部, 研究員 (20422694)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2020: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords排尿障害 / 脊髄損傷 / 神経栄養因子 / 代謝型グルタミン酸 / 膀胱 / 外尿道括約筋 / マウス / 神経栄養因子前駆体 / グルタミン酸受容体 / 神経成長因子 / グルタミン酸
Outline of Research at the Start

膀胱収縮と外尿道括約筋活動の協調運動に外尿道括約筋運動神経核におけるmGluR1とmGluR5の部分的な関与が必要であること、慢性脊損によりmGluR1とmGluR5の遺伝子と蛋白の発現様態と機能的役割に変化を来たすということ、その過程に膀胱と外尿道括約筋を制御する神経ネットワークにproNGF/p75信号伝達誘発のアポトーシス/神経可塑性変化が関与していること、そのアポトーシス/神経可塑性変化を阻止することにより排尿筋外尿道括約筋協調不全の発症を予防、もしくは緩和できることを検証する。

Outline of Final Research Achievements

Chronically spinal cord injured mice present detrusor-sphincter dyssynergia. In the meantime, there are some silent periods that show synergic activity of the bladder and external urethral sphincter during the bladder contraction (i.e., decreased urethral resistance), which lead to urine evacuation. In addition, the present study revealed that p75NTR plays important role in the mechanism associated with synergic activity of the bladder and external urethral sphincter in the plastic change after spinal cord injury.

Academic Significance and Societal Importance of the Research Achievements

慢性脊髄損傷は、排尿筋外尿道括約筋協調不全を惹起し、排尿障害を起こす。やがて腎機能不全を呈するようになり、時として生命を脅かす。膀胱内が異常な高圧状態になることを回避できるよう、膀胱収縮時には外尿道括約筋が弛緩し、尿道抵抗が減弱することが望ましい。
本研究では、脊髄損傷後に排尿筋外尿道括約筋協調不全を呈するメカニズムの一端を明らかにした。今回の研究成果が、将来的に、排尿筋外尿道括約筋協調不全を緩和し、膀胱と尿道の協調性のある活動へと導く治療法開発に役立つことが期待される。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (13 results)

All 2023 2022 2020 2019 Other

All Int'l Joint Research (6 results) Journal Article (3 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 3 results,  Open Access: 2 results) Presentation (1 results) (of which Int'l Joint Research: 1 results) Book (2 results) Remarks (1 results)

  • [Int'l Joint Research] オハイオ州立大学/バーモント大学(米国)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] Duke University/University of Conneticut(米国)

    • Related Report
      2021 Research-status Report
  • [Int'l Joint Research] Duke University/University of Connecticut/Harvard Medical School(米国)

    • Related Report
      2020 Research-status Report
  • [Int'l Joint Research] Lund University(スウェーデン)

    • Related Report
      2020 Research-status Report
  • [Int'l Joint Research] McGill University(カナダ)

    • Related Report
      2020 Research-status Report
  • [Int'l Joint Research] University of Kahramanmaras/University of Cukurova(トルコ)

    • Related Report
      2020 Research-status Report
  • [Journal Article] Best practices for cystometric evaluation of lower urinary tract function in muriform rodents2020

    • Author(s)
      Fraser, M.O., Smith, P.P., Sullivan, M.P., Bjorling, D.E., Campeau, L., Andersson, K.-E., Yoshiyama, M.
    • Journal Title

      Neurourology and Urodynamics

      Volume: 39 Issue: 6 Pages: 1868-1884

    • DOI

      10.1002/nau.24415

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Blockade of acid-sensing ion channels increases urinary bladder capacity with or without intravesical irritation in mice2020

    • Author(s)
      Yoshiyama, M., Kobayashi, H., Takeda, M., Araki, I.
    • Journal Title

      Frontiers in Physiology

      Volume: 11 Pages: 592867-592867

    • DOI

      10.3389/fphys.2020.592867

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The effect of Ferula elaeochytris root extract on erectile dysfunction in streptozotocin-induced diabetic rat2019

    • Author(s)
      Eser Nadire、Buyuknacar Hacer Sinem、Cimentepe Ozge Ozturk、Gocmen Cemil、Ucar Yilmaz、Erdogan Seyda、Yoshiyama Mitsuharu
    • Journal Title

      International Journal of Impotence Research

      Volume: 印刷中 Issue: 2 Pages: 186-194

    • DOI

      10.1038/s41443-019-0137-8

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Acid-sensing ion channel 3 (ASIC3) inhibitor increases functional bladder capacity with or without acidic irritation of lower urinary tract in mice when administering intraperitoneally but not intravesically2020

    • Author(s)
      Yoshiyama, M.
    • Organizer
      International Continence Society 2020 Online Meeting
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Book] Handbook of Neurourology: Theory and Practice2023

    • Author(s)
      YOSHIYAMA, Mitsuharu、KAKIZAKI, Hidehiro
    • Total Pages
      19
    • Publisher
      Springer Singapore
    • Related Report
      2022 Annual Research Report
  • [Book] Handbook of Neurourology: Theory and Practice2022

    • Author(s)
      Mitsuharu Yoshiyama, Hidehiro Kakizaki
    • Publisher
      Springer Nature
    • Related Report
      2021 Research-status Report
  • [Remarks] Translation of in vivo preclinical research

    • URL

      https://www.ics.org/live/16July21

    • Related Report
      2021 Research-status Report

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Published: 2020-04-28   Modified: 2024-01-30  

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