Autonomous circadian bladder capacity rhythm independent of the central clock

This study investigates the autonomous regulatory function of the bladder for its capacity circadian rhythm using a central nervous Bmal1 conditional knockout (cKO) mouse. Under constant darkness (DD), these mice lose behavioral rhythmicity but preserve rhythmicity of the bladder capacity and bladder clock gene expression for short term. However, prolonged exposure to DD results in loss of bladder capacity rhythm and decreased clock gene amplitude. RNA-seq analysis in the bladder of Bmal1 cKO mice revealed that clock genes and extracellular matrix-related genes were disrupted in rhythmicity under long DD. These findings highlight that the bladder has an autonomous regulatory function for the diurnal rhythm of bladder capacity independent of the central clock. However, the vulnerability of peripheral bladder clocks is revealed in the long-term absence of central clock input. This study provides molecular insights into how circadian dysregulation may contribute to bladder dysfunction.