A CO-EVOLUTIONARY THEORY OF SLEEP

Based on recent experimental evidence, a novel theory of sleep functio n and regulation is advanced, stating that sleep primarily evolved to protect the brain against a wakefulness-dependent increase in the perm eability of the blood-brain barrier. A restitutional mechanism for the blood-brain barrier had to co-evolve against the omnipresent gut-deri ved bacterial cell wall constituents, because these and their elicited cellular responses increase blood-brain barrier permeability and pote ntially harm nervous tissue. Thus, in order to develop a highly organi zed cerebral structure, an immune-like response specific for the brain co-evolved during the phylogeny of the symbiosis between animals and gut bacteria to control the detrimental effects of bacterial cell wall constituents. In the course of further evolution, the sleep-associate d 'controlled inflammatory state' of the brain employed the growth-fac tor activities of locally activated cytokines to enforce cerebral deve lopment and the maintenance of cognitive functions.