Molecular and Cellular Mechanisms of the Restorative Effects of Sleep

This article discusses current concepts of the role of sleep in cellular energy metabolism, the processes of neuroplasticity, and cleansing of the cerebral parenchyma from metabolic products. Numerous studies have demonstrated that prolonged waking poses a challenge to the brain, both energetically and physiologically. This article outlines the kinetics of the biochemical processes responsible for replenishing energy reserves during sleep. The roles of ATP, adenosine, and glycogen in these processes are noted. Depletion of the substrates of cellular energy metabolism leads to stress on the endoplasmic reticulum and protein-unfolding reactions. These changes are paralleled by increases in synaptic conductivity, which aggravates energy disorders because increases in the size and number of synapses imply increases in energy costs. The level of glymphatic clearance during waking is significantly lower than that during sleep, and metabolic products cannot be eliminated at the necessary rate.