Macromolecule biosynthesis: a key function of sleep

Abstract

The function(s) of sleep remains a major unanswered question in biology. We assessed changes in gene expression in the mouse cerebral cortex and hypothalamus following different durations of sleep and periods of sleep deprivation. There were significant differences in gene expression between behavioral states; we identified 3,988 genes in the cerebral cortex and 823 genes in the hypothalamus with altered expression patterns between sleep and sleep deprivation. Changes in the steady-state level of transcripts for various genes are remarkably common during sleep, as 2,090 genes in the cerebral cortex and 409 genes in the hypothalamus were defined as sleep specific and changed (increased or decreased) their expression during sleep. The largest categories of overrepresented genes increasing expression with sleep were those involved in biosynthesis and transport. In both the cerebral cortex and hypothalamus, during sleep there was upregulation of multiple genes encoding various enzymes involved in cholesterol synthesis, as well as proteins for lipid transport. There was also upregulation during sleep of genes involved in synthesis of proteins, heme, and maintenance of vesicle pools, as well as antioxidant enzymes and genes encoding proteins of energy-regulating pathways. We postulate that during sleep there is a rebuilding of multiple key cellular components in preparation for subsequent wakefulness.

Homer1a is a core brain molecular correlate of sleep loss

“…Again, the most significantly overexpressed gene after sleep deprivation was Homer1a, followed by those belonging to stress-response and synaptic-plasticity gene groups. The major functional gene groups that reduced their expression after sleep deprivation concern protein synthesis, membrane trafficking, and protein transport (SI Table 5) (12). Real-time quantitative RT-PCR verification for 41 candidate genes (found here and by others) at ZT6 confirmed our microarray findings at this reference time point (SI Table 6).…”

“…According to the Ensemble database (Mus musculus release 46), this region contains 33 known genes, 15 potential unknown coding sequences, and three pseudogenes. Among these, the short splice variant of the Homer1 (Homer1a) gene is the only transcript in the region that was previously reported to be among the up-regulated genes after sleep deprivation (11)(12)(13)(14). However, the specificity of this finding, compared with other gene expression changes after sleep loss, has not yet been established.…”

Changes in brain gene expression during migration in the white-crowned sparrow

“…Several studies suggest that BiP may also protect the cell against cell death by suppressing the accumulation of reactive oxygen species and by stabilizing mitochondrial function (Liu et al 1998;Lee et al 1999;Yu et al 1999). BiP has been demonstrated to increase following a few hours of sleep loss in the cerebral cortex of mice (Terao et al 2003;Naidoo et al 2005;Mackiewicz et al 2007) rats (Cirelli et al 2004;Terao et al 2006), in the head of fruit flies (Shaw et al 2000;Naidoo et al 2007), as well as in the telencephalon of the white-crowned sparrow (Jones et al 2007). However, its expression is not further increased in the rat cerebral cortex after long-term sleep deprivation relative to short-term sleep loss (Cirelli et al 2006).…”

Sleep and Development in Genetically Tractable Model Organisms

“…Nelson and Raizen 2013), so the involvement of sleep in this process lends credence to a hypothesized role for sleep in macromolecular biosynthesis (Mackiewicz et al 2007;Nelson and Raizen 2013). In addition, large-scale synaptic formation and rearrangement in C. elegans occur during development.…”