概日リズム障害と夜間頻尿

抄録

Since the discovery of clock genes and the identification of circadian oscillating factors around them, the concept of circadian rhythms surrounding us has changed dramatically. Clinical studies and basic research clock genes have revealed the mechanisms by which various factors cause circadian rhythm disorder due to abnormalities in clock genes. Jet lag, stress, and aging can also affect clock gene function, and the resulting circadian rhythm disorder can cause various diseases. Bladder function is also regulated by clock genes, and circadian rhythm disorders cause lower urinary tract disease such as nocturia. In this workshop, I will talk about clock genes and the circadian bladder function in mice, nocturia caused by abnormal clock genes, and its clinical applications.

Recently, the relationship between abnormalities in clock genes and nocturia has been reported. In humans, shift work and exposure to various stress cause circadian rhythm disorder, which leading to nocturia. In animals, clock genes regulate circadian function in the bladder smooth muscle and epithelium to produce circadian rhythms of bladder capacity and urinary perception. Mice with abnormal clock genes have a phenotype of nocturia, and loss of circadian rhythm in the bladder due to abnormal clock genes is thought to be the cause of nocturia.

In the mice bladder, stress-induced circadian rhythm disorder caused nocturia. In addition, drug-induced modification of the bladder's circadian rhythm also improved nocturia. Furthermore, metabolomics analysis of fatty acid metabolites in the blood of nocturia patients revealed a circadian rhythm of fatty acid metabolite associated with nocturia. These fatty acid metabolites have specific receptors and have also been found to be possibly involved in inducing the urinary reflex in the bladder.

The pathology of nocturia is complex and details are still unknown. Circadian rhythm disorders associated with clock genes may be one of the most important factors. The approach from the circadian rhythm of the bladder may have great potential in the development of new treatment for nocturia.