Zimmerman John E, Rizzo Wendy, Shockley Keith R, Raizen David M, Naidoo Nirinjini, Mackiewicz Miroslaw, Churchill Gary A, Pack Allan I
Center for Sleep and Respiratory Neurobiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
Physiol Genomics. 2006 Nov 27;27(3):337-50. doi: 10.1152/physiolgenomics.00030.2006. Epub 2006 Sep 5.
The functions of sleep and what controls it remain unanswered biological questions. According to the two-process model, a circadian process and a homeostatic process interact to regulate sleep. While progress has been made in understanding the molecular and cellular functions of the circadian process, the mechanisms of the homeostatic process remain undiscovered. We use the recently established sleep model system organism Drosophila melanogaster to examine dynamic changes in gene expression during sleep and during prolonged wakefulness in the brain. Our experimental design controls for circadian processes by killing animals at three matched time points from the beginning of the consolidated rest period [Zeitgeber time (ZT) 14)] under two conditions, sleep deprived and spontaneously sleeping. Using ANOVA at a false discovery rate of 5%, we have identified 252 genes that were differentially expressed between sleep-deprived and control groups in the Drosophila brain. Using linear trends analysis, we have separated the significant differentially expressed genes into nine temporal expression patterns relative to a common anchor point (ZT 14). The most common expression pattern is a decrease during extended wakefulness but no change during spontaneous sleep (n = 114). Genes in this category were involved in protein production (n = 47), calcium homeostasis, and membrane excitability (n = 5). Multiple mechanisms, therefore, act to limit wakefulness. In addition, by studying the effects of the mechanical stimulus used in our deprivation studies during the period when the animals are predominantly active, we provide evidence for a previously unappreciated role for the Drosophila immune system in the brain response to stress.
睡眠的功能以及控制睡眠的因素仍然是生物学中尚未解答的问题。根据双过程模型，昼夜节律过程和稳态过程相互作用来调节睡眠。虽然在理解昼夜节律过程的分子和细胞功能方面已经取得了进展，但稳态过程的机制仍未被发现。我们使用最近建立的睡眠模型系统生物果蝇来研究大脑在睡眠期间和长时间清醒期间基因表达的动态变化。我们的实验设计通过在两种条件下（睡眠剥夺和自然睡眠）从巩固休息期开始的三个匹配时间点（时间geber时间（ZT）14）处死动物来控制昼夜节律过程。使用错误发现率为5%的方差分析，我们在果蝇大脑中鉴定出252个在睡眠剥夺组和对照组之间差异表达的基因。使用线性趋势分析，我们将显著差异表达的基因相对于一个共同的锚定点（ZT 14）分为九种时间表达模式。最常见的表达模式是在延长清醒期间减少，但在自然睡眠期间没有变化（n = 114）。这一类别的基因参与蛋白质产生（n = 47）、钙稳态和膜兴奋性（n = 5）。因此，多种机制共同作用来限制清醒。此外，通过研究我们在剥夺研究中使用的机械刺激在动物主要活跃期间的影响，我们为果蝇免疫系统在大脑对应激反应中的一个先前未被认识到的作用提供了证据。
