Sleep is a therapeutic window for photostimulation of drainage of aging brain

Age is a limiting factor in the efficacy of photobiomodulation (PBM) for brain drainage and cognitive functions. Meningeal lymphatic vessels (MLVs) are "tunnels" for removal of toxins from the brain and the target of PBM. Age-related decline in the MLV functions is one of the mechanisms by which the effects of PBM on brain drainage and cognitive process are limited. Sleep is a time of natural activation of brain drainage. Recent findings have shown that PBM during sleep has greater effects on lymphatic clearance of beta-amyloid and cognitive function in young and middle-age mice. Based on these data, this study tested the hypothesis that sleep enhances the effects of PBM on MLVs and cognitive function in the aging brain. Indeed, the results revealed that PBM during sleep, but not during wakefulness, has stimulatory effects on lymphatic clearance of beta-amyloid from the brain of old mice that improves memory. In sleep deficit experiments, it was found that chronic sleep deprivation is accompanied by suppression of brain drainage and removal of metabolites from the brain, such as beta-amyloid, tau, glutamate, lactate and glucose in young, middle-aged and most significantly in old mice. The course of PBM during sleep contributed better than in wakefulness to the restoration of the brain level of tested metabolites in young and middle-aged mice, while in old mice only PBM during sleep was effective. These results open a new strategy for the use of PBM during sleep to improve the efficacy of PBM on clearance of toxic metabolites from the brain, especially in aged subjects in whom the efficacy of PBM during wakefulness is limited.