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A Molecular Window on Sleep: Changes in Gene Expression between Sleep and Wakefulness

Department of Psychiatry, University of Wisconsin-Madison, ccirelli{at}wisc.edu

Sleep is thought to be "by the brain and for the brain," but despite decades of behavioral and neurophysiologic research, we still do not know why the brain actually needs to sleep. Recently, gene expression studies have allowed researchers to investigate the molecular correlates of sleep and wakefulness and to gain new insights into the benefits that sleep may bring at the cellular level. In the latest series of studies, a genome-wide screening of brain gene expression was performed in rats that had been asleep, spontaneously awake, or sleep deprived for 8 hours. It was found that of ~15,000 transcripts expressed in the cerebral cortex, about 5% change their expression levels depending on behavioral state but independently of time of day. Half of the modulated genes increase in wakefulness and half in sleep. Moreover, wakefulness-related and sleep-related transcripts belong to different functional categories. Waking-related transcripts are involved in energy metabolism, excitatory neurotransmission, transcriptional activation, synaptic potentiation and memory acquisition, and the response to cellular stress. Sleep-related transcripts are involved in brain protein synthesis, synaptic consolidation/depression, and membrane trafficking and maintenance, including cholesterol metabolism, myelin formation, and synaptic vesicle turnover.

Key Words: Cerebral cortex • Locus coeruleus • Noradrenaline • Sleep deprivation • Synaptic plasticity

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