Changes in brain gene expression after long-term sleep deprivation
Changes in brain gene expression after long-term sleep deprivation
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DOI：
10.1111/j.1471-4159.2006.04058.x
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发表时间：
2006-09-01
影响因子：
4.7
通讯作者：
Tononi, Giulio
中科院分区：
文献类型：
--
作者：
Cirelli, Chiara;Faraguna, Ugo;Tononi, Giulio
长期睡眠剥夺会导致大鼠能量消耗增加、体重减轻以及2-3周后死亡等显著生理变化。尽管有几项研究，但睡眠剥夺综合症在很大程度上仍然没有得到解释。在这里，为了阐明长期失眠如何影响脑细胞，我们使用了微阵列，并筛选了大脑皮层中>；26000个转录本的表达。采用水盘法剥夺大鼠睡眠1周。75个转录本显示，与自然醒着或睡眠被剥夺了几个小时的对照组相比，这些动物的表达增加。其中大多数是由于慢性睡眠不足而引起的，而不是视盘刺激的非特异性影响。它们包括编码几种免疫球蛋白、应激反应蛋白(巨噬细胞抑制因子相关蛋白14、热休克蛋白27、α-B晶体蛋白)、米诺地尔磺基转移酶、珠蛋白和皮质抑素的转录本。在长期睡眠剥夺的大鼠中，有28个转录本降低了它们的表达。其中16个基因由于慢性睡眠不足而明显减少，其中包括编码I型前胶原和二氢硫胺乙酰转移酶的基因。我们还将睡眠大鼠与短期和长期睡眠剥夺的大鼠进行了比较，发现急性和慢性睡眠不足导致了分子水平上的一些差异。仅在急性睡眠剥夺后，几个可塑性相关基因被强烈诱导，几个神经胶质基因在两种睡眠剥夺条件下下调，但程度不同。这些发现表明，持续的睡眠不足可能会在大脑中引发广泛的炎症和应激反应。
Long-term sleep deprivation in rats produces dramatic physiological changes including increase in energy expenditure, decrease in body weight, and death after 2-3 weeks. Despite several studies, the sleep deprivation syndrome remains largely unexplained. Here, to elucidate how prolonged sleep loss affects brain cells we used microarrays and screened the expression of > 26 000 transcripts in the cerebral cortex. Rats were sleep deprived using the disk-over-water method for 1 week. Seventy-five transcripts showed increased expression in these animals relative to controls that had been spontaneously awake or sleep deprived for a few hours. Most of them were induced as a result of chronic sleep loss and not non-specific effects of the disk stimulation. They include transcripts coding for several immunoglobulins, stress response proteins (macrophage inhibitor factor-related protein 14, heat-shock protein 27, alpha-B-crystallin), minoxidil sulfotransferase, globins and cortistatin. Twenty-eight transcripts decreased their expression in long-term sleep-deprived rats. Sixteen of them were specifically decreased as a result of chronic sleep loss, including those coding for type I procollagen and dihydrolipoamide acetyltransferase. We also compared sleeping rats to short-term and long-term sleep-deprived rats, and found that acute and chronic sleep loss led to some differences at the molecular level. Several plasticity-related genes were strongly induced after acute sleep deprivation only, and several glial genes were down-regulated in both sleep deprivation conditions, but to a different extent. These findings suggest that sustained sleep loss may trigger a generalized inflammatory and stress response in the brain.