A Co-evolutionary theory of sleep

Based on recent experimental evidence, a novel theory of sleep function and regulation is advanced, stating that sleep primarily evolved to protect the brain against a wakefulness-dependent increase in the permeability of the blood-brain barrier. A restitutional mechanism for the blood-brain barrier had to co-evolve against the omnipresent gut-derived bacterial cell wall constituents, because these and their elicited cellular responses increase blood-brain barrier permeability and potentially harm nervous tissue. Thus, in order to develop a highly organized 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-associated ‘controlled inflammatory state’ of the brain employed the growth-factor activities of locally activated cytokines to enforce cerebral development and the maintenance of cognitive functions.