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Genomic analysis of sleep deprivation reveals translational regulation in the hippocampus

Cited 92 time in Web of Science Cited 105 time in Scopus
Authors

Vecsey, Christopher G.; Peixoto, Lucia; Choi, Jennifer H. K.; Wimmer, Mathieu; Jaganath, Devan; Hernandez, Pepe J.; Blackwell, Jennifer; Meda, Karuna; Park, Alan J.; Hannenhalli, Sridhar; Abel, Ted

Issue Date
2012-10
Publisher
AMER PHYSIOLOGICAL SOC
Citation
PHYSIOLOGICAL GENOMICS, Vol.44 No.20, pp.981-991
Abstract
Vecsey CG, Peixoto L, Choi JHK, Wimmer M, Jaganath D, Hernandez PJ, Blackwell J, Meda K, Park AJ, Hannenhalli S, Abel T. Genomic analysis of sleep deprivation reveals translational regulation in the hippocampus. Physiol Genomics 44: 981-991, 2012. First published August 28, 2012; doi:10.1152/physiolgenomics.00084.2012.-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.
ISSN
1094-8341
URI
https://hdl.handle.net/10371/203415
DOI
https://doi.org/10.1152/physiolgenomics.00084.2012
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Research Area Computational decoding, Electrophysiology, Neuroscience

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