Journal
SCIENCE ADVANCES
Volume 4, Issue 7, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.aat1294
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Funding
- Merck Research Laboratories
- Defense Advanced Research Projects Agency
- U.S. Army Research Office [W911NF-10-1006]
- National Institute of Mental Health of the NIH [F30MH106293]
- National Heart, Lung, and Blood Institute of the NIH [T32HL007909]
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To understand the transcriptomic organization underlying sleep and affective function, we studied a population of (C57BL/6J x 12951 /SvlmJ) F2 mice by measuring 283 affective and sleep phenotypes and profiling gene expression across four brain regions. We identified converging molecular bases for sleep and affective phenotypes at both the single-gene and gene-network levels. Using publicly available transcriptomic datasets collected from sleep deprived mice and patients with major depressive disorder (MDD), we identified three cortical gene networks altered by the sleep/wake state and depression. The network-level actions of sleep loss and depression were opposite to each other, providing a mechanistic basis for the sleep disruptions commonly observed in depression, as well as the reported acute antidepressant effects of sleep deprivation. We highlight one particular network composed of circadian rhythm regulators and neuronal activity-dependent immediate-early genes. The key upstream driver of this network, Arc, may act as a nexus linking sleep and depression. Our data provide mechanistic insights into the role of sleep in affective function and MDD.
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