Cirelli Chiara
Department of Psychiatry, University of Wisconsin/Madison, Madison, Wisconsin 53719, USA.
J Appl Physiol (1985). 2002 Jan;92(1):394-400. doi: 10.1152/jappl.2002.92.1.394.
The identification of the molecular correlates of sleep and wakefulness is essential to understand the restorative processes occurring during sleep, the cellular mechanisms underlying sleep regulation, and the functional consequences of sleep loss. To determine what molecular changes occur in the brain during the sleep-waking cycle and after sleep deprivation, our laboratory is performing a systematic screening of brain gene expression in rats that have been either sleeping or spontaneously awake for a few hours and in rats that have been sleep deprived for different periods of time ranging from a few hours to several days. So far, ~10,000 transcripts expressed in the cerebral cortex have been screened. The expression of the vast majority of these genes does not change either across behavioral states or after sleep deprivation, even when forced wakefulness is prolonged for several days. A few hours of wakefulness, either spontaneous or forced by sleep deprivation, increase the expression of the same small groups of genes: immediate-early genes/transcription factors, genes related to energy metabolism, growth factors/adhesion molecules, chaperones/heat shock proteins, vesicle- and synapse-related genes, neurotransmitter/hormone receptors, neurotransmitter transporters, and enzymes. Sleep, on the other hand, induces the expression of a few unknown transcripts whose characterization is in progress. Thus, although the characterization of the molecular correlates of behavioral states is not yet complete, it is already apparent that the transition from sleep to waking can affect basic cellular functions such as RNA and protein synthesis, neural plasticity, neurotransmission, and metabolism. The pattern of changes in gene expression after long periods of sleep deprivation is unique and does not resemble that of short-term sleep deprivation or spontaneous wakefulness. A notable exception is represented, however, by the enzyme arylsulfotransferase, whose induction appears to be proportional to the duration of previous wakefulness. Arylsulfotransferase in rodents plays a major role in the catabolism of catecholamines, suggesting that an important role for sleep may be that of interrupting the continuous activity, during wakefulness, of brain catecholaminergic systems.
识别睡眠与清醒的分子关联对于理解睡眠期间发生的恢复过程、睡眠调节的细胞机制以及睡眠剥夺的功能后果至关重要。为了确定在睡眠 - 清醒周期以及睡眠剥夺后大脑中发生了哪些分子变化，我们的实验室正在对大鼠进行系统的脑基因表达筛选，这些大鼠分别处于睡眠或自发清醒数小时的状态，以及被剥夺不同时长（从数小时到数天）睡眠的状态。到目前为止，已经筛选了在大脑皮层中表达的约10,000个转录本。这些基因中的绝大多数在行为状态改变或睡眠剥夺后都不会发生变化，即使强制清醒延长数天也是如此。数小时的清醒，无论是自发的还是因睡眠剥夺导致的，都会增加同一小群基因的表达：即早基因/转录因子、与能量代谢相关的基因、生长因子/黏附分子、伴侣蛋白/热休克蛋白、与囊泡和突触相关的基因、神经递质/激素受体、神经递质转运体以及酶。另一方面，睡眠会诱导一些未知转录本的表达，其特征正在研究中。因此，尽管行为状态的分子关联特征尚未完全明确，但已经很明显，从睡眠到清醒的转变会影响诸如RNA和蛋白质合成、神经可塑性、神经传递和代谢等基本细胞功能。长时间睡眠剥夺后的基因表达变化模式是独特的，与短期睡眠剥夺或自发清醒的模式不同。然而，一个显著的例外是芳基硫酸转移酶，其诱导似乎与先前清醒的持续时间成正比。啮齿动物中的芳基硫酸转移酶在儿茶酚胺分解代谢中起主要作用，这表明睡眠的一个重要作用可能是中断清醒期间大脑儿茶酚胺能系统的持续活动。
