Exercise and the Neural Circadian System

良好的睡眠习惯和规律的体育锻炼是健康长寿的基石。睡眠-觉醒周期是由大脑的生物钟组织的。这个大脑区域的细胞包含一个分子钟，但必须相互通信才能产生统一的~24小时输出，从而控制其他大脑区域和身体器官。这些单独的时钟细胞通过一种叫做神经肽的特殊大脑化学物质进行交流，每种物质在计时中都有自己的作用。通常情况下，大脑生物钟细胞会在日光下被重置，但有趣的是，在一个老鼠模型中，大脑生物钟因缺乏一种特殊的神经肽信号而被削弱，我们发现，有规律的日常体育锻炼比光照更有效。在我们的工作中，我们发现在跑步轮中自愿安排的锻炼（每天6小时）可以同步时钟细胞，并促进稳定的~24小时休息-活动节律。这种有趣的运动效果在老鼠身上是不存在的，因为老鼠的大脑和身体的所有细胞都没有分子钟。不幸的是，我们不知道体育锻炼是否可以弥补其他种类神经肽的损失或大脑时钟中特定类型神经肽细胞分子钟的缺失。我们也不知道是否大脑的其他区域接收到来自大脑时钟的计时信号有助于这些恢复运动的行为。在这项资助中，我们将解决这些知识上的重要空白，并确定自愿体育锻炼如何改善大脑的同步，从而促进健康。

Good sleep habits and regular physical exercise are a cornerstone of good health and longevity. The sleep-wake cycle is organised by the brain's daily or circadian clock. Cells of this brain area contain a molecular clock but must talk to each other to produce a unified ~24h output that controls other brain areas as well as body organs. These individual clock cells communicate using special brain chemicals called neuropeptides, each of which has its own role in timekeeping. Ordinarily, brain clock cells are reset by daylight, but interestingly, in a mouse model in which the brain clock was weakened by through the absence of a particular neuropeptide signal, we found that regular daily physical exercise was much more potent than light. In our work, we found that voluntary scheduled exercise in a running-wheel (6h/day) synchronises the clock cells and promotes stable ~24h rest-activity rhythms. This intriguing effect of exercise was absent in mice in which the molecular clock was deleted from all cells of the brain and body. Unfortunately, we do not know if physical exercise can compensate for the loss of other kinds of neuropeptides or the absence of the molecular clock in particular types of neuropeptide cells in brain clock. We also do not know if other areas of the brain receiving timekeeping signals from the brain clock contribute to these restorative actions of exercise. In this grant we shall address these important gaps in our knowledge and determine how voluntary physical exercise can improve synchronisation in the brain to promote well-being.