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

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K18086
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56030:Urology-related
• Research Institution: University 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
• Keywords: 膀胱 / 概日時計 / 排尿 / 睡眠 / 日内リズム

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.

Free Research Field

泌尿器

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。