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2015 Fiscal Year Annual Research Report

慢性脊損後排尿障害に関連する神経ペプチドと代謝型グルタミン酸信号伝達の可塑性変化

Research Project

Project/Area Number 25462507
Research InstitutionUniversity of Yamanashi

Principal Investigator

芳山 充晴  山梨大学, 総合研究部, 医学研究員 (20422694)

Co-Investigator(Kenkyū-buntansha) 吉良 聡  山梨大学, 総合研究部, 助教 (10530115)
Project Period (FY) 2013-04-01 – 2016-03-31
Keywords下部尿路機能 / 膀胱 / 外尿道括約筋 / マウス / 排尿障害 / 脊髄損傷 / 興奮性グルタミン酸受容体 / 神経ペプチド
Outline of Annual Research Achievements

代謝型グルタミン酸受容体サブタイプ1a(mGluR1a)遺伝子欠損(KO)マウスと野生型(WT)マウスの排尿機能を比較した。代謝ケージを用いた自発排尿行動評価において、WTと比較してKOは一日排尿回数が少なく、一回排尿量が多かった。シストメトリー法を用いた排尿反射評価では、KOマウスは一回排尿量、膀胱容量が著しく多く、最大排尿収縮圧が高く、排尿効率が有意に低下していた。過去の研究と併せこれらの結果は、mGluR1aは膀胱からの興奮性求心性信号伝達、及び、外尿道括約筋への興奮性入力の抑制性制御に関与することを示唆した。
WT脊損マウスとKO脊損マウスの下部尿路機能を膀胱内圧測定と外尿道括約筋筋電図を用いて比較した。WTに比し、KOは排尿筋外尿道括約筋協調不全が更に著しかった。WT脊損マウスにmGluR5拮抗薬を投与すると膀胱収縮時の排尿筋外尿道括約筋協調不全発生の頻度が増加した。以上の結果は、脊損後排尿困難において、mGluR1a、及び、mGluR5を介する神経信号伝達が排尿筋外尿道括約筋協調不全に抗して作用していることを示す。
以上の研究成果は、American Urological Association Annual Meeting、European Urological Association Annual Congress、International Continence Society Annual Meeting、日本排尿機能学会で発表した。研究アイディアの一部は、国際共同研究に反映され、論文として発表した(American Journal of Physiology)。

  • Research Products

    (15 results)

All 2016 2015 Other

All Int'l Joint Research (1 results) Journal Article (2 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 2 results,  Acknowledgement Compliant: 1 results) Presentation (12 results) (of which Int'l Joint Research: 8 results)

  • [Int'l Joint Research] University of Pittsburgh(U.S.A.)

    • Country Name
      U.S.A.
    • Counterpart Institution
      University of Pittsburgh
  • [Journal Article] Characterization of bladder and external urethral activity in mice with or without spinal cord injury - a comparison study with rats2016

    • Author(s)
      Kadekawa K, Yoshimura N, Majima T, Wada N, Shimizu T, Birder LA, Kanai AJ, de Groat WC, Sugaya K, Yoshiyama M
    • Journal Title

      American Journal of Physiology Regulatory Integrative Comparative Physiology

      Volume: 310 Pages: R752-R758

    • DOI

      10.1152/ajpregu.00450.2015

    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Functional roles of TRPV1 and TRPV4 in control of lower urinary tract activity: dual analysis of behavior and reflex during the micturition cycle2015

    • Author(s)
      Yoshiyama M, Mochizuki T, Nakagomi H, Miyamoto T, Kira S, Mizumachi R, Sokabe T, Takayama Y, Tominaga M, Takeda M
    • Journal Title

      American Journal of Physiology Renal Physiology

      Volume: 308 Pages: F1128-F1134

    • DOI

      10.1152/ajprenal.00016.2015

    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] Clock genes regulate circadian rhythm of Piezo1 and TRPV4 expressions and intracellular Ca2+ influx after stretch stimulation in the cultured urothelial cells2016

    • Author(s)
      Tatsuya Ihara,Satoru Kira,Tatsuya Miyamoto,Norifumi Sawada,Hiroshi Nakagomi,Takahiko Mitsui,Hideki Kobayashi,Mitsuharu Yoshiyama,Masayuki Takeda,Yuki Nakamura,Atsuhito Nakao,Eiji Shigetomi,Keisuke Shibata,Youichi Shinozaki,Syuichi Koizumi
    • Organizer
      The 31st Annual Congress of the European Association of Urology
    • Place of Presentation
      Munich, Germany
    • Year and Date
      2016-03-13
    • Int'l Joint Research
  • [Presentation] Metabotropic glutamate receptor subtypes 1 and 5 synergistically modulate bladder filling function in mice2016

    • Author(s)
      Mitsuharu Yoshiyama,Masayuki Takeda
    • Organizer
      The 31st Annual Congress of the European Association of Urology
    • Place of Presentation
      Munich, Germany
    • Year and Date
      2016-03-13
    • Int'l Joint Research
  • [Presentation] The long-term effect of a special programme of pelvic floor muscle training for female patients with LUTS in Japan2015

    • Author(s)
      Tamami Taniguchi,Hideki Kobayashi,Takahiko Mitsui,Mitsuharu Yoshiyama,Masayuki Takeda
    • Organizer
      International Continence Society 45th Annual meeting
    • Place of Presentation
      Montreal, Canada
    • Year and Date
      2015-10-08
    • Int'l Joint Research
  • [Presentation] Investigation of LUTS (lower urinary tract symptoms) with pelvic organ prolapse (cystocele)2015

    • Author(s)
      Hideki Kobayashi,Tamami Taniguchi,Yuko Ootake,Satoru Kira,Takahiko Mitsui,Hidenori Zakoji,Mitsuiharu Yoshiyama,Masayuki Takeda
    • Organizer
      International Continence Society 45th Annual meeting
    • Place of Presentation
      Montreal, Canada
    • Year and Date
      2015-10-08
    • Int'l Joint Research
  • [Presentation] Clock mutant mouse is a novel experimental model for nocturia/nocturnal polyuria2015

    • Author(s)
      Tatsuya Ihara,Satoru Kira,Takashi Yamagishi,Tatsuya Miyamoto,Norifumi Sawada,Mitsuharu Yoshiyama,Masayuki Takeda,Yuki Nakamura,Atsuhito Nakao
    • Organizer
      International Continence Society 45th Annual meeting
    • Place of Presentation
      Montreal, Canada
    • Year and Date
      2015-10-07
    • Int'l Joint Research
  • [Presentation] Characterization of bladder and external urethral sphincter activity in mice with or withut spinal cord injury – a comparison study with rats2015

    • Author(s)
      Katsumi Kadekawa,Mitsuharu Yoshiyama,Tsuyoshi Majima,Naoki Wada,Takahiro Shimizu,William C. de Groat,Kimio Sugaya            ,
    • Organizer
      International Continence Society 45th Annual meeting
    • Place of Presentation
      Montreal, Canada
    • Year and Date
      2015-10-07
    • Int'l Joint Research
  • [Presentation] Roles of metabotropic glutamate receptor subtype 1a in lower urinary tract function of mice2015

    • Author(s)
      Mitsuharu Yoshiyama,Tsutomu Mochizuki,Masayuki Takeda
    • Organizer
      International Continence Society 45th Annual meeting
    • Place of Presentation
      Montreal, Canada
    • Year and Date
      2015-10-07
    • Int'l Joint Research
  • [Presentation] 過去3年間の過活動膀胱患者におけるミラベグロン服薬継続率:性差、単独と併用の比較2015

    • Author(s)
      武田正之、内山秀行、志村寛史、青木 正、大竹裕子、座光寺秀典、宮本達也、三井貴彦、小林英樹、芳山充晴
    • Organizer
      第22回日本排尿機能学会
    • Place of Presentation
      京王プラザホテル札幌、北海道札幌市
    • Year and Date
      2015-09-10
  • [Presentation] 時計遺伝子異常による膀胱上皮Piezo1発現の変化と排尿への影響2015

    • Author(s)
      井原達矢、吉良 聡、山岸 敬、宮本達也、澤田智史、三井貴彦、芳山充晴、武田正之
    • Organizer
      第22回日本排尿機能学会
    • Place of Presentation
      京王プラザホテル札幌、北海道札幌市
    • Year and Date
      2015-09-10
  • [Presentation] 代謝型グルタミン酸受容体1aサブタイプ欠損マウスの下部尿路機能評価2015

    • Author(s)
      芳山充晴、望月 勉、武田正之
    • Organizer
      第22回日本排尿機能学会
    • Place of Presentation
      京王プラザホテル札幌、北海道札幌市
    • Year and Date
      2015-09-09
  • [Presentation] Functional roles of metabotropic glutamate receptor subtype 1a in control of lower urinary tract activity in mice2015

    • Author(s)
      Mitsuharu Yoshiyama,Tsutomu Mochizuki,Masayuki Takeda
    • Organizer
      American Urological Association Annual Meeting
    • Place of Presentation
      New Orleans, Louisiana, U.S.A.
    • Year and Date
      2015-05-16
    • Int'l Joint Research
  • [Presentation] マウス膀胱平滑筋・上皮におけるP2Y6受容体機能の検討2015

    • Author(s)
      吉良 聡、芳山充晴、宮本達也、井原達矢、中込宙史、望月 勉、柴田圭輔、繁冨 英治、小泉修一、武田正之
    • Organizer
      第103回日本泌尿器科学会
    • Place of Presentation
      ホテル金沢、石川県金沢市
    • Year and Date
      2015-04-19

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Published: 2017-01-06  

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