Maret Stéphanie, Dorsaz Stéphane, Gurcel Laure, Pradervand Sylvain, Petit Brice, Pfister Corinne, Hagenbuchle Otto, O'Hara Bruce F, Franken Paul, Tafti Mehdi
Center for Integrative Genomics and Lausanne DNA Array Facility, University of Lausanne, Génopode, CH-1015 Lausanne, Switzerland.
Proc Natl Acad Sci U S A. 2007 Dec 11;104(50):20090-5. doi: 10.1073/pnas.0710131104. Epub 2007 Dec 6.
Sleep is regulated by a homeostatic process that determines its need and by a circadian process that determines its timing. By using sleep deprivation and transcriptome profiling in inbred mouse strains, we show that genetic background affects susceptibility to sleep loss at the transcriptional level in a tissue-dependent manner. In the brain, Homer1a expression best reflects the response to sleep loss. Time-course gene expression analysis suggests that 2,032 brain transcripts are under circadian control. However, only 391 remain rhythmic when mice are sleep-deprived at four time points around the clock, suggesting that most diurnal changes in gene transcription are, in fact, sleep-wake-dependent. By generating a transgenic mouse line, we show that in Homer1-expressing cells specifically, apart from Homer1a, three other activity-induced genes (Ptgs2, Jph3, and Nptx2) are overexpressed after sleep loss. All four genes play a role in recovery from glutamate-induced neuronal hyperactivity. The consistent activation of Homer1a suggests a role for sleep in intracellular calcium homeostasis for protecting and recovering from the neuronal activation imposed by wakefulness.
睡眠由一个决定其需求的稳态过程和一个决定其时间的昼夜节律过程调节。通过在近交系小鼠品系中使用睡眠剥夺和转录组分析，我们发现遗传背景在转录水平上以组织依赖的方式影响对睡眠缺失的易感性。在大脑中，Homer1a的表达最能反映对睡眠缺失的反应。时间进程基因表达分析表明，2032个脑转录本受昼夜节律控制。然而，当小鼠在昼夜四个时间点被剥夺睡眠时，只有391个转录本仍保持节律性，这表明基因转录中的大多数昼夜变化实际上是依赖于睡眠-觉醒的。通过构建一个转基因小鼠品系，我们发现，特别是在表达Homer1的细胞中，除了Homer1a之外，另外三个活动诱导基因（Ptgs2、Jph3和Nptx2）在睡眠缺失后也会过度表达。这四个基因都在从谷氨酸诱导的神经元过度兴奋中恢复的过程中发挥作用。Homer1a的持续激活表明睡眠在细胞内钙稳态中具有作用，以保护神经元免受觉醒引起的激活并从中恢复。
