Genomic analysis of sleep deprivation reveals translational regulation in the hippocampus.

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TitleGenomic analysis of sleep deprivation reveals translational regulation in the hippocampus.
Publication TypeJournal Article
Year of Publication2012
AuthorsVecsey, CG, Peixoto, L, Choi, JHK, Wimmer, M, Jaganath, D, Hernandez, PJ, Blackwell, J, Meda, K, Park, AJ, Hannenhalli, S, Abel, T
JournalPhysiol Genomics
Volume44
Issue20
Pagination981-91
Date Published2012 Oct 17
ISSN1531-2267
KeywordsAnimals, Computational Biology, Gene Expression Regulation, Genomics, Hippocampus, Insulin, Male, Memory, Mice, Mice, Inbred C57BL, Oligonucleotide Array Sequence Analysis, Protein Array Analysis, Protein Biosynthesis, Signal Transduction, Sleep Deprivation, Time Factors, TOR Serine-Threonine Kinases
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.

DOI10.1152/physiolgenomics.00084.2012
Alternate JournalPhysiol. Genomics
PubMed ID22930738
PubMed Central IDPMC3472468
Grant ListT32HL-007953 / HL / NHLBI NIH HHS / United States
K12GM-081259 / GM / NIGMS NIH HHS / United States
P50AG-017628 / AG / NIA NIH HHS / United States
NS-007413 / NS / NINDS NIH HHS / United States
HL-07953 / HL / NHLBI NIH HHS / United States
R01GM-085226 / GM / NIGMS NIH HHS / United States
MH-090711 / MH / NIMH NIH HHS / United States
P01 AG017628 / AG / NIA NIH HHS / United States
GM-07517 / GM / NIGMS NIH HHS / United States
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