Journal article
Genomic analysis of sleep deprivation reveals translational regulation in the hippocampus
Physiological genomics, Vol.44(20), pp.981-991
10/15/2012
Handle:
https://hdl.handle.net/2376/109938
PMCID: PMC3472468
PMID: 22930738
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.
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Details
- Title
- Genomic analysis of sleep deprivation reveals translational regulation in the hippocampus
- Creators
- Christopher G Vecsey - Department of Biology, Brandeis University, Waltham, MassachusettsLucia Peixoto - Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania; andJennifer H. K Choi - Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania; andMathieu Wimmer - Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania; andDevan Jaganath - Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania; andPepe J Hernandez - Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania; andJennifer Blackwell - Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania; andKaruna Meda - Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania; andAlan J Park - Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania; andSridhar Hannenhalli - Department of Cell and Molecular Biology, University of Maryland, College Park, MarylandTed Abel - Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania; and
- Publication Details
- Physiological genomics, Vol.44(20), pp.981-991
- Academic Unit
- Biomedical Sciences, Department of
- Publisher
- American Physiological Society; Bethesda, MD
- Grant note
- GM-07517; HL-07953; MH-090711; NS-007413; T32HL-007953; K12GM-081259; P50AG-017628; R01GM-085226 / National Institutes of Health
- Identifiers
- 99900547217101842
- Language
- English
- Resource Type
- Journal article