The FASEB J：机体时钟基因异常或可解释膀胱过度活动症的发病原因

  如果你认为睡眠问题和膀胱问题是个体老年肯定会出现的问题，那么你就说对了；近日，发表在国际杂志The FASEB Journal上的一篇研究论文中，来自萨里大学的研究人员表示，我们的醒睡周期或许和膀胱存在遗传上的关联，一方受破坏或许就会引发另一方受影响，于是研究者们就假设，在正常情况下大脑中的主生物钟可以控制机体许多其它的次要生物钟，这些次要的生物钟随后会控制功能性蛋白及受体的活性，这就包括膀胱中的功能性蛋白的活性。

  Changhao Wu博士说道，我们希望这项研究可以增强理解机体的昼夜节律控制及年龄相关的机体异常，从而为通过靶向作用机体的昼夜节律调节过程来开发新型疾病疗法提供希望；文章中研究者利用遗传修饰小鼠进行研究，当从离体的膀胱组织中产生时钟蛋白时就会有特殊的光波长被释放，这些光就会实时报道小鼠机体时钟的表达，并且可以直接测量小鼠机体次要的时钟表达。

  超过24小时后，在受体激活子存在或不存在时，时钟表达的改变都会被记录下来；而膀胱壁中节律时钟活性24小时都会发生，尤其在大约12小时的时候会达到高峰，受体激活子会转移机体对早期时间的时钟表达，在老年小鼠体内，时钟的表达及其对激活子的效应都受到了明显的抑制。研究者表示，膀胱的收缩同样也表现出了小鼠机体的昼夜节律，这类似于时钟表达的改变。

  膀胱的收缩功能可以通过局部的昼夜节律钟来改变，而机体时钟的相互控制对于维持机体次要器官的功能具有重要的作用，机体时钟功能的异常则会引发年龄相关的障碍发生，比如膀胱过度活动症的发生，最后研究者Gerald Weissmann表示，膀胱过度活动症破坏了许多个体的日常生活，尤其是对个体的睡眠及旅行过程，本文研究为揭示引发膀胱过度活动症的原因及开发新型的靶向疗法提供了新的线索和依据。（转化医学网360zhyx.com）
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Local receptors as novel regulators for peripheral clock expression
The FASEB Journal doi: 10.1096/fj.13-243295
Changhao Wu*,1, Guiping Sui†, Simon N. Archer*, Paolo Sassone-Corsi‡, Karen Aitken§, Darius Bagli§ and Ying Chen*
Mammalian circadian control is determined by a central clock in the brain suprachiasmatic nucleus (SCN) and synchronized peripheral clocks in other tissues. Increasing evidence suggests that SCN-independent regulation of peripheral clocks also occurs. We examined how activation of excitatory receptors influences the clock protein PERIOD 2 (PER2) in a contractile organ, the urinary bladder. PERIOD2::LUCIFERASE-knock-in mice were used to report real-time PER2 circadian dynamics in the bladder tissue. Rhythmic PER2 activities occurred in the bladder wall with a cycle of ∼24 h and peak at ∼12 h. Activation of the muscarinic and purinergic receptors by agonists shifted the peak to an earlier time (7.2±2.0 and 7.2±0.9 h, respectively). PER2 expression was also sensitive to mechanical stimulation. Aging significantly dampened PER2 expression and its response to the agonists. Finally, muscarinic agonist-induced smooth muscle contraction also exhibited circadian rhythm. These data identified novel regulators, endogenous receptors, in determining local clock activity, in addition to mediating the central control. Furthermore, the local clock appears to reciprocally align receptor activity to circadian rhythm for muscle contraction. The interaction between receptors and peripheral clock represents an important mechanism for maintaining physiological functions and its dysregulation may contribute to age-related organ disorders.—Wu, C., Sui, G., Archer, S. N., Sassone-Corsi, P., Aitken, K., Bagli, D., Chen, Y. Local receptors as novel regulators for peripheral clock expression.