title: Genomic analysis of sleep deprivation reveals translational regulation in the hippocampus.
abstract: Sleep deprivation is a common problem of considerable health and economic impact in today's society. Sleep loss is associated with deleterious effects on cognitive functions such as memory and has a high comorbidity with many neurodegenerative and neuropsychiatric disorders. Therefore, it is crucial to understand the molecular basis of the effect of sleep deprivation in the brain. In this study, we combined genome-wide and traditional molecular biological approaches to determine the cellular and molecular impacts of sleep deprivation in the mouse hippocampus, a brain area crucial for many forms of memory. Microarray analysis examining the effects of 5 h of sleep deprivation on gene expression in the mouse hippocampus found 533 genes with altered expression. Bioinformatic analysis revealed that a prominent effect of sleep deprivation was to downregulate translation, potentially mediated through components of the insulin signaling pathway such as the mammalian target of rapamycin (mTOR), a key regulator of protein synthesis. Consistent with this analysis, sleep deprivation reduced levels of total and phosphorylated mTOR, and levels returned to baseline after 2.5 h of recovery sleep. Our findings represent the first genome-wide analysis of the effects of sleep deprivation on the mouse hippocampus, and they suggest that the detrimental effects of sleep deprivation may be mediated by reductions in protein synthesis via downregulation of mTOR. Because protein synthesis and mTOR activation are required for long-term memory formation, our study improves our understanding of the molecular mechanisms underlying the memory impairments induced by sleep deprivation.
authors.affiliation: Department of Biology, Brandeis University, Waltham, Massachusetts, USA.
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Vecsey
authors.forename: Lucia
authors.initials: L
authors.lastname: Peixoto
authors.forename: Jennifer H K
authors.initials: JH
authors.lastname: Choi
authors.forename: Mathieu
authors.initials: M
authors.lastname: Wimmer
authors.forename: Devan
authors.initials: D
authors.lastname: Jaganath
authors.forename: Pepe J
authors.initials: PJ
authors.lastname: Hernandez
authors.forename: Jennifer
authors.initials: J
authors.lastname: Blackwell
authors.forename: Karuna
authors.initials: K
authors.lastname: Meda
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Park
authors.forename: Sridhar
authors.initials: S
authors.lastname: Hannenhalli
authors.forename: Ted
authors.initials: T
authors.lastname: Abel
mesh_terms: D000818:Animals; D019295:Computational Biology / Q000379:methods; D005786:Gene Expression Regulation; D023281:Genomics; D006624:Hippocampus / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D008297:Male; D008568:Memory; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D040081:Protein Array Analysis / Q000379:methods*; D014176:Protein Biosynthesis; D015398:Signal Transduction; D012892:Sleep Deprivation / Q000235:genetics*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D013997:Time Factors
chemical_list: D007328:Insulin; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases