Presence of multiple peripheral circadian oscillators in the tissues controlling voiding function in mice

Circadian clocks are the endogenous oscillators that harmonize a variety of physiological processes within the body. Although many urinary functions exhibit clear daily or circadian variation in diurnal humans and nocturnal rodents, the precise mechanisms of these variations are as yet unclear. In the present study, we demonstrate that Per2 promoter activity clearly oscillates in neonate and adult bladders cultured ex vivo from Per2 ::Luc knock-in mice. In subsequent experiments, we show that multiple local oscillators are operating in all the bladder tissues (detrusor, sphincter and urothelim) and the lumbar spinal cord (L4–5) but not in the pontine micturition center or the ventrolateral periaqueductal gray of the brain. Accordingly, the water intake and urine volume exhibited daily and circadian variations in young adult wild-type mice but not in Per1 −/− Per2 −/− mice, suggesting a functional clock-dependent nature of the micturition rhythm. Particularly in PDK mice, the water intake and urinary excretion displayed an arrhythmic pattern under constant darkness, and the amount of water consumed and excreted significantly increased compared with those of WT mice. These results suggest that local circadian clocks reside in three types of bladder tissue and the lumbar spinal cord and may have important roles in the circadian control of micturition function. Circadian biology: Genetic clocks control urination patterns Molecular clocks found in the bladder and spine help to regulate the daily rhythms of urination, according to a mouse study from researchers in South Korea. Sehyung Cho, a physiologist at Kyung Hee University in Seoul, and his colleagues measured the expression patterns of Per2 and other known clock-related genes in cultured mouse bladders and in living mice. They found that clock gene activity oscillated in a circadian fashion in all three types of bladder tissue and in the lumbar spinal cord. They found no such clock-like activity, however, in mouse tissue taken from brain regions involved in the neural control of urinary function. In mouse models deficient for these clock-related genes, the researchers also observed arrhythmic patterns of water intake and urinary excretion when the animals were kept in constant darkness.