Plastic changes in transmission of neuropeptide and metabotropic glutamate related to voiding dysfunction after chronic spinal cord injury

• Project/Area Number: 25462507
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Urology
• Research Institution: University of Yamanashi
• Principal Investigator: YOSHIYAMA Mitsuharu 山梨大学, 総合研究部, 医学研究員 (20422694)
• Co-Investigator(Kenkyū-buntansha): KIRA Satoru 山梨大学, 総合研究部, 助教 (10530115)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2013: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• 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 / 外尿道括約筋活動 / 膀胱活動 / 下部尿路機能制御 / 慢性脊髄損傷 / 代謝型グルタミン酸

Outline of Final Research Achievements

We compared the lower-urinary-tract function of the wild type (WT) spinal cord injured mouse and the metabotropic glutamate receptor subtype 1a (mGluR1a-KO) gene deficit spinal cord injured mouse, using a cystometrogram and external urethral sphincter (EUS) electromyogram (EMG). The mGluR1a-KO presented more marked detrusor-sphincter dyssynergia (DSD) compared with WT. The mGluR5 antagonist increased the occurrence rate of DSD in the WT spinal cord injured mouse. The above results suggest that the neural transmission via mGluR1a and mGluR5 is involved in anti-DSD in urinary voiding dysfunction after spinal cord injury.

Research Products

• [Int'l Joint Research] University of Pittsburgh(U.S.A.)
• [Journal Article] Characterization of bladder and external urethral activity in mice with or without spinal cord injury - a comparison study with rats (2016)
  • 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 Issue: 8 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 cycle (2015)
  • 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 Issue: 10 Pages: F1128-F1134
  • DOI: 10.1152/ajprenal.00016.2015
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Effects of urethane on reflex activity of lower urinary tract in decerebrate unanesthetized rats (2013)
  • Author(s): Mitsuharu Yoshiyama
  • Journal Title: American Journal of Physiology - Renal Physiology Volume: 304 Issue: 4 Pages: F390-F396
  • DOI: 10.1152/ajprenal.00574.2012
  • Peer Reviewed
• [Journal Article] Expression of large conductance, voltage- and Ca2+-activated K+ (BK) channels in human urinary bladder: alteration of subunit expression profile in association with bladder outlet obstruction (2013)
  • Author(s): Zakoji, H., Kobayashi, H., Yoshiyama, M., Takeda, M., Araki, I.
  • Journal Title: Open Journal of Urology Volume: 3 Issue: 02 Pages: 47-52
  • DOI: 10.4236/oju.2013.32009
  • Peer Reviewed
• [Journal Article] Distribution and possible function of cannabinoid receptor subtype 1 in the human prostate (2013)
  • Author(s): Kamiyama, M., Fukasawa, M., Takihana, Y., Sawada, N., Nakagomi, H., Yoshiyama, M., Araki, I., Takeda, M.
  • Journal Title: Open Journal of Urology Volume: 3 Issue: 02 Pages: 102-109
  • DOI: 10.4236/oju.2013.32020
  • Peer Reviewed
• [Journal Article] 中枢性グルタミン酸，モノアミン作動性下部尿路機能制御 (2013)
  • Author(s): 芳山充晴
  • Journal Title: 山梨医科学誌 Volume: 28(1) Pages: 17-29
  • NAID: 110009623367
  • Peer Reviewed
• [Presentation] Clock genes regulate circadian rhythm of Piezo1 and TRPV4 expressions and intracellular Ca2+ influx after stretch stimulation in the cultured urothelial cells (2016)
  • 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 mice (2016)
  • 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 Japan (2015)
  • 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 polyuria (2015)
  • 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 rats (2015)
  • 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 mice (2015)
  • 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 mice (2015)
  • 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
• [Presentation] P2Y6受容体は膀胱蓄尿機能に関与している (2014)
  • Author(s): 吉良聡
  • Organizer: 第87回日本薬理学会年会
  • Place of Presentation: 東北大学百周年記念会館川内萩ホール、仙台国際センター（宮城県仙台市）
• [Presentation] Metabotropic glutamate receptor subtype 5 antagonist facilitates urine storage without impairing micturition in mice (2013)
  • Author(s): Mitsuharu Yoshiyama
  • Organizer: American Urological Association Annual Meeting
  • Place of Presentation: San Diego Convention Center（San Diego, California, U.S.A）.
• [Presentation] Neither systemic nor intravesical administration of A-317567, an acid-sensing ion channel blocker affect the lower urinary tract activity in decerebrate unanesthetized mice (2013)
  • Author(s): Mitsuharu Yoshiyama
  • Organizer: International Continence Society 43rd Annual meeting
  • Place of Presentation: Centre Convencions Internacional de Barcelona（Barcelona,Spain)
• [Presentation] 膀胱上皮・排尿筋・末梢神経を標的にした下部尿路機能障害治療薬の開発 (2013)
  • Author(s): 芳山充晴
  • Organizer: 第20回日本排尿機能学会
  • Place of Presentation: 静岡コンベンションアーツセンター、グランシップ（静岡県静岡市）
  • Invited
• [Presentation] Efficacy of the beta3-adrenoceptor agonist mirabegron in patients with stress urinary incontinence (2013)
  • Author(s): Hideki Kobayashi
  • Organizer: International Continence Society 43rd Annual meeting
  • Place of Presentation: Centre Convencions Internacional de Barcelona,(Barcelona,Spain)
• [Presentation] Metabortopic glutamate receptor subtype 5 antagonist increases bladder capacity without impairing voiding in decerebrate unanesthetized mice (2013)
  • Author(s): Mitsuharu Yoshiyama
  • Organizer: The 8th Pan=pacific Continence Society Meeting
  • Place of Presentation: BEXCO (Busan Exhibition & Convention Center)(Busan, Korea)
• [Presentation] Efficacy of the beta3-adrenoceptor agonist mirabegron in patients with stress urinary incontinence (2013)
  • Author(s): Hideki Kobayashi
  • Organizer: The 8th Pan=pacific Continence Society Meeting
  • Place of Presentation: BEXCO (Busan Exhibition & Convention Center)(Busan, Korea)
• [Presentation] Urethroplasty for the difficult cases of anterior urethral stricture (2013)
  • Author(s): Hidenori Zakoji
  • Organizer: The 8th Pan=pacific Continence Society Meeting
  • Place of Presentation: BEXCO (Busan Exhibition & Convention Center)(Busan, Korea)