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Mechanism of Action# Cortistatin's sleep-promoting mechanism is better characterized than DSIP's: Cortical synchronization -- promotes EEG synchronization that characterizes slow-wave sleep, selectively enhancing deep sleep without affecting REM sleep or total sleep time Cholinergic antagonism -- reduces cortical arousal by antagonizing acetylcholine-mediated excitation, effectively dampening the wake-promoting cholinergic system Homeostatic sleep regulation -- preprocortistatin mRNA expression follows a circadian rhythm and is upregulated after sleep deprivation, suggesting cortistatin functions as an endogenous homeostatic sleep factor BDNF-dependent expression -- brain-derived neurotrophic factor regulates cortistatin expression in an activity-dependent manner, linking it to sleep homeostasis Cortistatin has a unique dual receptor profile