Modulation of brain gene expression during sleep and wakefulness: A reviewof recent findings

The characterization of the molecular correlates of sleep and wakefulness i s essential to understand the restorative processes occurring during sleep and the cellular mechanisms underlying sleep regulation. In order to determ ine what molecular changes occur during the sleep-waking cycle, we have rec ently performed a systematic screening of gene expression in the brain of s leeping, sleep deprived, and spontaneously awake rates. Out of the similar to 10,000 genes screened so far, a small minority (similar to0.5%) was diff erentially expressed in the cerebral cortex across behavioral states. Most genes were upregulated in wakefulness and sleep deprivation relative to sle ep, while only a few, were upregulated in sleep relative to wakefulness and sleep deprivation. Almost all the genes upregulated in sleep, and several genes upregulated in wakefulness and sleep deprivation, did not match any k nown sequence. Known genes expressed at higher levels in wakefulness and sl eep deprivation could be grouped into functional categories: immediate earl y genes transcription factors, genes related to energy metabolism, growth f actors/adhesion molecules, chaperones/heat shock proteins, vesicle and syna pse-related genes, neurotransmitter/hormone receptors, neurotransmitter tra nsporters, enzymes, and others. Although the characterization of the molecu lar correlates of sleep, wakefulness, and sleep deprivation is still in pro gress, it is already apparent that the transition from sleep to waking can affect basic cellular functions such as RNA and protein synthesis, neural p lasticity, neurotransmission, and metabolism. (C) 2001 American College of Neuropsychopharmacology. Published by Elsevier Science Inc.