Rapid alterations in cortical protein profiles underlie spontaneous sleep and wake bouts

Existing data indicate that sleep-wakefulness is an essential behavior. The biological function(s) of sleep, however, remains unknown, due, in part, to the lack of information available at the intracellular level. Preliminary microarray analyses show that changes in behavioral state influence regional mRNA profiles; however, the impact of sleep on protein signatures is virtually unexplored. In these studies, cortical protein profiles were examined after timed bouts of spontaneous sleep-wakefulness. Within minutes of each behavioral state examined, a small number of spots showing unique expression were detected. Mass spectroscopy analyses of sleep- and wake-related spots identified proteins associated with multiple functional categories. Two sleep-associated proteins were further validated using a sleep deprivation paradigm. We found preliminary evidence for two different post-transcriptional mechanisms-one (GAPDH) in which the amount of protein was increased in the recovery sleep following prolonged waking, while the other (actin) suggested that post-translational modifications may underlie sleep. The similarities between the effects of sleep on both protein and mRNA profiles indicate that dynamic intracellular changes underlie sleep-wake states and are consistent with roles for sleep in multiple biological functions.