Meerlo P, Koehl M, van der Borght K, Turek F W
Department of Neurobiology and Physiology, Northwestern University, Evanston, IL, USA.
J Neuroendocrinol. 2002 May;14(5):397-402. doi: 10.1046/j.0007-1331.2002.00790.x.
Chronic sleep restriction is an increasing problem in many countries and may have many, as yet unknown, consequences for health and well being. Studies in both humans and rats suggest that sleep deprivation may activate the hypothalamic-pituitary-adrenal (HPA) axis, one of the main neuroendocrine stress systems. However, few attempts have been made to examine how sleep loss affects the HPA axis response to subsequent stressors. Furthermore, most studies applied short-lasting total sleep deprivation and not restriction of sleep over a longer period of time, as often occurs in human society. Using the rat as our model species, we investigated: (i) the HPA axis activity during and after sleep deprivation and (ii) the effect of sleep loss on the subsequent HPA response to a novel stressor. In one experiment, rats were subjected to 48 h of sleep deprivation by placing them in slowly rotating wheels. Control rats were placed in nonrotating wheels. In a second experiment, rats were subjected to an 8-day sleep restriction protocol allowing 4 h of sleep each day. To test the effects of sleep loss on subsequent stress reactivity, rats were subjected to a 30-min restraint stress. Blood samples were taken at several time points and analysed for adrenocorticotropic hormone (ACTH) and corticosterone. The results show that ACTH and corticosterone concentrations were elevated during sleep deprivation but returned to baseline within 4 h of recovery. After 1 day of sleep restriction, the ACTH and corticosterone response to restraint stress did not differ between control and sleep deprived rats. However, after 48 h of total sleep deprivation and after 8 days of restricted sleep, the ACTH response to restraint was significantly reduced whereas the corticosterone response was unaffected. These results show that sleep loss not only is a mild activator of the HPA axis itself, but also affects the subsequent response to stress. Alterations in HPA axis regulation may gradually appear under conditions of long total sleep deprivation but also after repeated sleep curtailment.
慢性睡眠限制在许多国家正成为一个日益严重的问题，可能对健康和幸福产生许多尚未可知的后果。对人类和大鼠的研究表明，睡眠剥夺可能会激活下丘脑-垂体-肾上腺（HPA）轴，这是主要的神经内分泌应激系统之一。然而，很少有人尝试研究睡眠不足如何影响HPA轴对后续应激源的反应。此外，大多数研究采用的是短期的完全睡眠剥夺，而不是像人类社会中经常出现的那样在较长时间内限制睡眠。我们以大鼠作为模型物种，研究了：（i）睡眠剥夺期间及之后的HPA轴活性，以及（ii）睡眠不足对后续HPA对新应激源反应的影响。在一个实验中，将大鼠置于缓慢旋转的轮子上，使其遭受48小时的睡眠剥夺。对照大鼠置于不旋转的轮子上。在第二个实验中，大鼠接受为期8天的睡眠限制方案，每天允许4小时睡眠。为了测试睡眠不足对后续应激反应性的影响，对大鼠施加30分钟的束缚应激。在几个时间点采集血样，分析促肾上腺皮质激素（ACTH）和皮质酮。结果表明，睡眠剥夺期间ACTH和皮质酮浓度升高，但在恢复4小时内恢复到基线水平。睡眠限制1天后，对照大鼠和睡眠剥夺大鼠对束缚应激的ACTH和皮质酮反应没有差异。然而，在完全睡眠剥夺48小时后以及限制睡眠8天后，对束缚的ACTH反应显著降低，而皮质酮反应未受影响。这些结果表明，睡眠不足不仅是HPA轴本身的轻度激活剂，还会影响后续的应激反应。在长期完全睡眠剥夺的情况下，以及反复缩短睡眠时间后，HPA轴调节的改变可能会逐渐出现。
