Chronic sleep restriction disrupts interendothelial junctions in the hippocampus and increases blood-brain barrier permeability.

Abstract

Chronic sleep loss in the rat increases blood-brain barrier permeability to Evans blue and FITC-dextrans in almost the whole brain and sleep recovery during short periods restores normal blood-brain barrier permeability. Sleep loss increases vesicle density in hippocampal endothelial cells and decreases tight junction protein expression. However, at the ultrastructural level the effect of chronic sleep loss on interendothelial junctions is unknown. In this study we characterised the ultrastructure of interendothelial junctions in the hippocampus, the expression of tight junction proteins, and quantified blood-brain barrier permeability to fluorescein-sodium after chronic sleep restriction. Male Wistar rats were sleep restricted using the modified multiple platform method during 10 days, with a daily schedule of 20-h sleep deprivation plus 4-h sleep recovery at their home-cages. At the 10th day hippocampal samples were obtained immediately at the end of the 20-h sleep deprivation period, and after 40 and 120 min of sleep recovery. Samples were processed for transmission electron microscopy and western blot. Chronic sleep restriction increased blood-brain barrier permeability to fluorescein-sodium, and decreased interendothelial junction complexity by increasing the frequency of less mature end-to-end and simply overlap junctions, even after sleep recovery, as compared to intact controls. Chronic sleep loss also induced the formation of clefts between narrow zones of adjacent endothelial cell membranes in the hippocampus. The expression of claudin-5 and actin decreased after chronic sleep loss as compared to intact animals. Therefore, it seems that chronic sleep loss disrupts interendothelial junctions that leads to blood-brain barrier hyperpermeability in the hippocampus.