VA Boston Healthcare System, Research Service and Harvard Medical School, Department of Psychiatry, 940 Belmont St., Brockton, MA 02301-5596, USA.
Brain Res. 2013 Sep 19;1531:9-16. doi: 10.1016/j.brainres.2013.07.048. Epub 2013 Aug 2.
Sleep responses to chronic sleep restriction may be very different from those observed after acute total sleep deprivation. Specifically, when sleep restriction is repeated for several consecutive days, animals express attenuated compensatory increases in sleep time and intensity during daily sleep opportunities. The neurobiological mechanisms underlying these adaptive, or more specifically, allostatic, changes in sleep homeostasis are unknown. Several lines of evidence indicate that norepinephrine may play a key role in modulating arousal states and NREM EEG delta power, which is widely recognized as a marker for sleep intensity. Therefore, we investigated time course changes in brain adrenergic receptor mRNA levels in response to chronic sleep restriction using a rat model. Here, we observed that significantly altered mRNA levels of the α1- adrenergic receptor in the basal forebrain as well as α2- and β1-adrenergic receptor in the anterior cingulate cortex only on the first sleep restriction day. On the other hand, the frontal cortex α1-, α2-, and β1-adrenergic receptor mRNA levels were reduced throughout the period of sleep restriction. Combined with our earlier findings on EEG that sleep time and intensity significantly increased only on the first sleep restriction days, these results suggest that alterations in the brain norepinephrine system in the basal forebrain and cingulate cortex may mediate allostatic changes in sleep time and intensity observed during chronic sleep restriction.
慢性睡眠限制对睡眠的反应可能与急性完全睡眠剥夺后观察到的反应非常不同。具体来说，当睡眠限制连续几天重复时，动物在日常睡眠机会中表现出睡眠时间和强度的代偿性增加减弱。睡眠稳态的这些适应性变化（更具体地说是适应变化）的神经生物学机制尚不清楚。有几条证据表明，去甲肾上腺素可能在调节觉醒状态和 NREM EEG 德尔塔功率方面发挥关键作用，NREM EEG 德尔塔功率被广泛认为是睡眠强度的标志物。因此，我们使用大鼠模型研究了慢性睡眠限制对大脑肾上腺素能受体 mRNA 水平的时间进程变化。在这里，我们观察到，在睡眠限制的第一天，基底前脑的 α1-肾上腺素能受体以及前扣带皮层的 α2-和 β1-肾上腺素能受体的 mRNA 水平显著改变。另一方面，额叶皮质的 α1-、α2-和 β1-肾上腺素能受体 mRNA 水平在整个睡眠限制期间都降低了。结合我们之前关于 EEG 的发现，即只有在睡眠限制的第一天，睡眠时间和强度才会显著增加，这些结果表明，基底前脑和扣带皮层的大脑去甲肾上腺素系统的改变可能介导了慢性睡眠限制期间观察到的睡眠时间和强度的适应变化。
