title: Presence of multiple peripheral circadian oscillators in the tissues controlling voiding function in mice.
abstract: 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.
authors.affiliation: Department of Neuroscience & Neurodegeneration Control Research Center, Kyung Hee University, Seoul, Korea.
authors.forename: Jong-Yun
authors.initials: JY
authors.lastname: Noh
authors.affiliation: Department of Neuroscience & Neurodegeneration Control Research Center, Kyung Hee University, Seoul, Korea.
authors.forename: Dong-Hee
authors.initials: DH
authors.lastname: Han
authors.affiliation: Department of Neuroscience & Neurodegeneration Control Research Center, Kyung Hee University, Seoul, Korea.
authors.forename: Mi-Hee
authors.initials: MH
authors.lastname: Kim
authors.affiliation: Department of Physiology, Kyung Hee University School of Medicine, Seoul, Korea.
authors.forename: Il-Gyu
authors.initials: IG
authors.lastname: Ko
authors.affiliation: Department of Physiology, Kyung Hee University School of Medicine, Seoul, Korea.
authors.forename: Sung-Eun
authors.initials: SE
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences, Seoul National University, Seoul, Korea.
authors.forename: Noheon
authors.initials: N
authors.lastname: Park
authors.affiliation: Department of Biological Sciences, Seoul National University, Seoul, Korea.
authors.forename: Han Kyoung
authors.initials: HK
authors.lastname: Choe
authors.affiliation: Department of Urology, Gachon University Gil Hospital, Gachon University of Medicine and Science, Incheon, Korea.
authors.forename: Khae-Hawn
authors.initials: KH
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences, Seoul National University, Seoul, Korea.
authors.forename: Kyungjin
authors.initials: K
authors.lastname: Kim
authors.affiliation: Department of Physiology, Kyung Hee University School of Medicine, Seoul, Korea.
authors.forename: Chang-Ju
authors.initials: CJ
authors.lastname: Kim
authors.affiliation: 1] Department of Neuroscience & Neurodegeneration Control Research Center, Kyung Hee University, Seoul, Korea [2] Department of Physiology, Kyung Hee University School of Medicine, Seoul, Korea.
authors.forename: Sehyung
authors.initials: S
authors.lastname: Cho
mesh_terms: D000818:Animals; D057906:Circadian Clocks; D004326:Drinking; D051379:Mice; D009928:Organ Specificity; D010487:Periaqueductal Gray / Q000378:metabolism / Q000502:physiology; D056950:Period Circadian Proteins / Q000235:genetics / Q000378:metabolism*; D011149:Pons / Q000378:metabolism / Q000502:physiology; D013116:Spinal Cord / Q000378:metabolism* / Q000502:physiology; D001743:Urinary Bladder / Q000294:innervation / Q000378:metabolism / Q000502:physiology*; D014554:Urination
chemical_list: C539023:Per1 protein, mouse; C513312:Per2 protein, mouse; D056950:Period Circadian Proteins