Omics Approaches in Sleep-Wake Regulation

Abstract

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.

Phosphorylation Hypothesis of Sleep

“…It is well understood that most of the transcriptome profile is under the control of circadian clocks ( Reppert and Weaver, 2002 ). Accordingly, researchers have attempted to find genes in which the expression pattern shows daily rhythmicity and changes upon the accumulation of sleep need (e.g., sleep deprivation condition) ( Elliott et al, 2014 ; O’Callaghan et al, 2019 ). However, advances in next-generation sequencing and mass spectrometer-based -omics technologies indicate that the gene expression pattern does not always reflect the expression pattern of gene products ( Figure 2 ).…”

The role of sleep and wakefulness in myelin plasticity

“…This indicates that sleep must serve some fundamental functions for the organism, some of which remain to be fully elucidated (Cirelli and Tononi, ). Much of what we have learnt about sleep's cellular consequences comes from two decades of gene expression studies, which highlighted differences in gene transcription between the two major behavioral states: sleep and wake (Cirelli and Tononi, ; Cirelli et al, , , ; Terao et al, ; Maret et al, ; Mongrain et al, ; Vecsey et al, ; O'Callaghan et al, ). Interestingly, these studies consistently highlight that genes implicated in the maintenance of cellular plasma membranes are preferability transcribed during sleep suggesting that, perhaps, one of the functions of sleep could be to maintain healthy plasma membranes.…”

Sleep Physiology, Circadian Rhythms, Waking Performance and the Development of Sleep-Wake Therapeutics

“…Sleep is a major determinant of well-being, mental and physical health and understanding sleep-health relations, and sleep disorders are dependent on adequate quantification of sleep. Sleep and wake states are characterised by constellations of variables representing nearly all levels of system organisation ranging from gene expression (O'Callaghan et al 2018), neuronal firing patterns (McKillop and Vyazovskiy 2018), neurotransmitter release (Zant et al 2016;Luppi and Fort 2018), endocrine and autonomic nervous system status (Morris et al 2012;Fink et al 2018), body and brain temperature (Landolt et al 1995), responsiveness to external stimuli (Ermis et al 2010), motor behaviour (Horner and Peever 2017) to changes in consciousness (Casali et al 2013). Which variables are essential to sleep quality and how these variables contribute to sleep's associations with well-being, physical health and brain function remain, however, largely unknown even though several hypotheses have been proposed.…”