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日常生物钟组织起来的。这个脑区的细胞包含一个分子钟，但必须相互交谈才能产生统一的~24小时的输出，控制其他脑区以及身体器官。这些单独的时钟细胞使用被称为神经肽的特殊大脑化学物质进行通信，每种神经肽都有自己的守时作用。通常情况下，大脑时钟细胞会在白天重新设置，但有趣的是，在一个大脑时钟因缺乏特定神经肽信号而被削弱的小鼠模型中，我们发现日常规律的体育锻炼比光更有效。在我们的工作中，我们发现自愿的有计划的跑轮运动(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。在大脑和身体的所有细胞中分子钟都被删除的小鼠身上，运动的这种有趣的效果是不存在的。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，或者大脑时钟中特定类型神经肽细胞分子时钟的缺失。我们也不知道大脑的其他区域接收来自大脑时钟的计时信号是否有助于运动的这些恢复性行为。在这笔赠款中，我们将解决我们知识中的这些重要差距，并确定自愿体育锻炼如何改善大脑的同步性，以促进幸福感。

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.