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Investigation into the mechanism of lower urinary tract dysfunction due to sleep disorder focusing on bladder clock

Research Project

Project/Area Number 20K18086
Research Category

Grant-in-Aid for Early-Career Scientists

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

Principal Investigator

Negoro Hiromitsu  筑波大学, 医学医療系, 准教授 (80708595)

Project Period (FY) 2020-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2020: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords膀胱 / 概日時計 / 排尿 / 睡眠 / 日内リズム / 睡眠障害 / 時間生物学 / 下部尿路症状
Outline of Research at the Start

排尿困難や夜間頻尿などの下部尿路症状は年齢とともにその頻度は増加し、高齢化社会の日本にとって対応は急務です。下部尿路症状の大規模かつ縦断的な疫学調査の解析にて、睡眠障害が排尿障害の強いリスク因子となることが判明しました。しかし、睡眠障害が排尿障害を引き起こすメカニズムは不明です。体内時計が排尿に関わっていることがわかってきており、本研究では、体内時計の破綻が排尿障害を引き起こすことを分子生物学的・生理学的に明らかとすることで、排尿障害の予防・治療につなげることを目的としています。

Outline of Final Research Achievements

We analyzed the effects of chronic sleep disorder on voiding function at the active phase, focusing on the diurnal rhythm of bladder capacity. In the mouse model of chronic sleep disorder, the urine voided volume per micturition (UVVM) during the active phase was decreased, the diurnal rhythm of UVVM was shifted 4-hour forward, and the diurnal rhythm of glucocorticoid was similarly shifted. Comprehensive analysis of variable genes by RNA-seq of the bladder confirmed a significant alteration of muscle-related gene clusters. Cellular experiments in vitro also revealed the presence of glucocorticoid as a bladder clock entrainer.
These results suggest that the chronic sleep disorder may cause a decrease in the voided volume per micturition at the active phase due to decreased activity of bladder smooth muscle, which, together with impairment of the bladder clock modulated by glucocorticoid, may lead to dysuria.

Academic Significance and Societal Importance of the Research Achievements

睡眠障害と排尿障害の関連が疫学調査から見出されたが、その機序は不明であった。睡眠障害モデルマウスの結果から、グルココルチコイドによる膀胱時計機能障害とともに、膀胱平滑筋の機能低下が介在することが考えられ、睡眠障害に起因する排尿障害の予防や新たな治療ターゲットに繋がることが期待される。

Report

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

    (10 results)

All 2022 2021 Other

All Int'l Joint Research (1 results) Journal Article (3 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (5 results) (of which Invited: 5 results) Book (1 results)

  • [Int'l Joint Research] Albert Einstein College of Medicine(米国)

    • Related Report
      2020 Research-status Report
  • [Journal Article] 特集 朝まで待てない! 夜間頻尿完全マスター 〈夜間頻尿の疫学と病態〉 サーカディアンリズムと夜間頻尿2021

    • Author(s)
      根来宏光
    • Journal Title

      臨床泌尿器科

      Volume: 75 Issue: 1 Pages: 36-41

    • DOI

      10.11477/mf.1413207098

    • ISSN
      0385-2393, 1882-1332
    • Year and Date
      2021-01-20
    • Related Report
      2021 Annual Research Report 2020 Research-status Report
  • [Journal Article] Diurnal rhythms of urine volume and electrolyte excretion in healthy young men under differing intensities of daytime light exposure.2021

    • Author(s)
      Nakamoto I, Uiji S, Okata R, Endo H, Tohyama S, Nitta R, Hashimoto S, Matsushima Y, Wakimoto J, Hashimoto S, Nishiyama Y, Kanikowska D, Negoro H, Wakamura T
    • Journal Title

      Sci Rep

      Volume: 11 Issue: 1 Pages: 13097-13097

    • DOI

      10.1038/s41598-021-92595-0

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Urothelium-Specific Deletion of Connexin43 in the Mouse Urinary Bladder Alters Distension-Induced ATP Release and Voiding Behavior2021

    • Author(s)
      Kono Jin、Ueda Masakatsu、Sengiku Atsushi、Suadicani Sylvia O.、Ogawa Osamu、Negoro Hiromitsu
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Issue: 4 Pages: 1594-1594

    • DOI

      10.3390/ijms22041594

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 時間薬理学・時間治療の最新の知見 『腎泌尿器科疾患の時間治療』2021

    • Author(s)
      根来宏光
    • Organizer
      第42回日本臨床薬理学会学術総会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 排尿障害研究の魅力2021

    • Author(s)
      根来宏光
    • Organizer
      第109回泌尿器科学会総会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 夜間頻尿と夜尿:概日リズムの視点から2021

    • Author(s)
      根来宏光
    • Organizer
      第73回西日本泌尿器科学会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 夜間頻尿診療の最適化2021

    • Author(s)
      根来宏光
    • Organizer
      第86回日本泌尿器科学会東部総会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 概日リズムの破綻から夜尿と夜間頻尿を考える2021

    • Author(s)
      根来宏光
    • Organizer
      第29回日本小児泌尿器科学会総会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Book] 適正使用のための臨床時間薬理学 生体リズムと薬物治療効果2022

    • Author(s)
      根来宏光
    • Total Pages
      6
    • Publisher
      診断と治療社
    • ISBN
      9784787824844
    • Related Report
      2021 Annual Research Report

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

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