Clock gene dysregulation may explain overactive bladder — ScienceDaily

By | October 31, 2014

“We hope our study will stimulate further progress in understanding circadian control of body physiology and aging-related dysfunction and ultimately lead to new strategies of treatment by targeting the circadian regulatory process, including non-drug treatment approaches,” said Changhao Wu, M.D., Ph.D., a researcher involved in the work from the Department of Biochemistry and Physiology at the University of Surrey in the United Kingdom.

To make this discovery, scientists used genetically modified mice in which a special wavelength of light was emitted when the clock proteins were produced in isolated bladder tissue. This light reported real-time clock expression and acted directly as a measure of peripheral clock expression. Over 24 hours, changes in clock expression were recorded in the presence and absence of the receptor activators. Rhythmic clock activities occurred in the bladder wall with a cycle around 24 hours and peaked at about hour 12. Application of these receptor activators shifted the peak of the clock expression to an earlier time. In older mice, the clock expression and its response to the activators were significantly dampened. Bladder contractions also exhibited circadian rhythms, similar to changes of the clock expression. The contractile function in the bladder can be regulated by the local circadian clocks, which are in turn under the feedback control of the output receptors. This reciprocal control of clock function represents an important mechanism for maintaining physiological function in the peripheral hollow organs and its dysregulation may contribute to abnormal motility in age-related disorders such as overactive bladder.

“It’s hard to appreciate how much of a problem an overactive bladder can be,” said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. “It disrupts many aspects of life, from the obvious, like sleep and travel, to the less obvious, like exercise and entertainment. This study helps us understand what’s causing the problem, and points the way to a solution.”

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