自主性運動改善睡眠剝奪所造成之負面影響

Abstract

在現今繁忙的社會中，睡眠不足或被干擾的情況常是無可避免的。許多報告指出，缺乏睡眠會影響學習及記憶等認知功能。因此，尋找能預防睡眠剝奪(sleep deprivation)所造成之腦部功能異常的對策，是非常重要的。而另一方面，運動可促進身體健康以及有益認知功能，是眾所皆知的。因此，我們想探討自主性運動 (voluntary exercise)是否可以預防睡眠剝奪後所造成之負面影響。本實驗使用出生後四週的雄性小鼠，這階段相似於人類的兒童到青少年時期。我們將小鼠分為少動及運動兩組。運動組小鼠的籠子裡放有轉輪，可讓小鼠自由地運動。少動組的籠內則無轉輪。飼養四週之後，兩組小鼠再各被分為正常睡眠組以及72 小時睡 眠剝奪組。因此，本實驗有個四組別：少動－正常睡眠組、少動－睡眠剝奪組、 運動－正常睡眠組以及運動－睡眠剝奪組。在開放空間(open field)的實驗當中，我們發現睡眠剝奪後，小鼠的活動力(locomotor activity)下降。然而，在新物體辨識(novel object recognition)，這個與短期記憶有關的實驗中，少動－睡眠剝奪組的小鼠無法辨識新舊物體，但運動－睡眠剝奪組小鼠，則表現得與少動－正常睡眠組及運動－正常睡眠組相似，皆可以辨識新舊物體。這些結果顯示，四週的自主性運動，對於睡眠剝奪所造成的認知功能缺失有保護效果。另一方面，我們檢測氧化壓力指標谷胱甘肽(glutathione)、大腦衍生神經營養因子(brain-derived neurotrophy factor, BDNF)以及海馬迴中神經新生的情形，顯示睡眠剝奪會造成氧化壓力上升、大腦衍生神經營養因子與神經新生減少。最後，我們檢驗與辨識記憶功能有關的腦區中神經元的結構。結果發現，在少動－睡眠剝奪組小鼠的齒狀迴(dentate gyrus)中，顆粒細胞(granule cells)之樹突的複雜度(complexity)，以及樹突棘(dendritic spines)的密度，較少動－正常睡眠組為低。在少動－睡眠剝奪組小鼠的中前額葉皮質(medial prefrontal cortex)中，也發現突棘密度減少。然而這些樹突結構結構上的異常，並未在運動－睡眠剝奪組被觀察到，這顯示四週的自主運動，亦在睡眠剝奪對樹突結構的損害上，有保護效果。總結來說，本研究結果顯示，自主性運動可以預防睡眠剝奪所造成之負面影響。

In our daily life, sleep deprivation (SD) or disturbances are somewhat inevitable.It is documented that sleep loss impairs cognitive functions such as learning and memory. Finding ways to prevent SD-related brain dysfunction is important.Voluntary exercise, a well-known health-promoting practice, is beneficial in various aspects including cognitive functions. We therefore hypothesized that voluntary exercise could counteract the negative effects following SD. To test this hypothesis, postweaning male mice were group-housed in cages with or without running wheels as exercise and sedentary groups, respectively. After 4 weeks, mice in both groups were subjected to normal sleep (NS) or 72-hour SD paradigm. Four groups of mice,sedentary-normal sleep (SNS), sedentary-sleep deprivation (SSD), exercise-normal sleep (ENS), and exercise-sleep deprivation (ESD), were then examined with various tasks. The level of locomotor activity in a novel open field was affected by SD. In addiation, the performance of short-term memory evaluated in novel object recognition test was impaired in SSD mice, but not in ESD mice, indicating the protective effect of voluntary exercise. The levels of glutathione (GSH) and brain-derived neurotrophy factor (BDNF) as well as the activity of hippocampal neurogenesis were significant decreased in SSD group, but not in ESD group. Morphologically, the dendritic architecture of the granule neurons in the dentate gyrus(DG) and layer II/III pyramidal neurons in the medial prefrontal cortex (mPFC) which are involved in recognition memory function was examined. In mice of SSD group,the dendritic complexity of DG granule cells was significantly reduced than those in SNS group. The spine density of DG and mPFC neurons in SSD group was also decreased. However, these structure changes were not observed in mice of ESD group,indicating a protective effect of exercise on SD-induced dendritic deficits. Together, these results demonstrated preventive effects of voluntary exercise on SD-induced negativities in mice.