O'Callaghan Emma K, Green Edward W, Franken Paul, Mongrain Valérie
Center for Advanced Research in Sleep Medicine and Research Center, Hôpital du Sacré-Coeur de Montréal, Montreal, QC, Canada.
Department of Neuroscience, Université de Montréal, Montreal, QC, Canada.
Handb Exp Pharmacol. 2019;253:59-81. doi: 10.1007/164_2018_125.
Although sleep seems an obvious and simple behaviour, it is extremely complex involving numerous interactions both at the neuronal and the molecular levels. While we have gained detailed insight into the molecules and neuronal networks responsible for the circadian organization of sleep and wakefulness, the molecular underpinnings of the homeostatic aspect of sleep regulation are still unknown and the focus of a considerable research effort. In the last 20 years, the development of techniques allowing the simultaneous measurement of hundreds to thousands of molecular targets (i.e. 'omics' approaches) has enabled the unbiased study of the molecular pathways regulated by and regulating sleep. In this chapter, we will review how the different omics approaches, including transcriptomics, epigenomics, proteomics, and metabolomics, have advanced sleep research. We present relevant data in the framework of the two-process model in which circadian and homeostatic processes interact to regulate sleep. The integration of the different omics levels, known as 'systems genetics', will eventually lead to a better understanding of how information flows from the genome, to molecules, to networks, and finally to sleep both in health and disease.
尽管睡眠看似是一种明显且简单的行为，但它极其复杂，涉及神经元和分子层面的众多相互作用。虽然我们已经深入了解了负责昼夜节律性睡眠和清醒的分子及神经元网络，但睡眠调节稳态方面的分子基础仍然未知，也是大量研究工作的重点。在过去20年里，能够同时测量数百到数千个分子靶点的技术（即“组学”方法）的发展，使得对受睡眠调节和调节睡眠的分子途径进行无偏倚研究成为可能。在本章中，我们将回顾不同的组学方法，包括转录组学、表观基因组学、蛋白质组学和代谢组学，如何推动了睡眠研究。我们在昼夜节律和稳态过程相互作用以调节睡眠的双过程模型框架内呈现相关数据。不同组学水平的整合，即“系统遗传学”，最终将有助于更好地理解信息如何从基因组流向分子、网络，最终影响健康和疾病状态下的睡眠。
