Investigation into the mechanism of lower urinary tract dysfunction due to sleep disorder focusing on bladder clock
| Project/Area Number |
20K18086
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 56030:Urology-related
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| Research Institution | University of Tsukuba |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| 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)
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| 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 |
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| 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。
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| 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.
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| 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。
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Report
(3 results)
Research Products
(10 results)
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[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
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Journal Title
Sci Rep
Volume: 11
Issue: 1
Pages: 13097-13097
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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