Glutamate, Glutamate Transporters, and Circadian Rhythm Sleep Disorders in Neurodegenerative Diseases.

Abstract

Glutamate, a primary excitatory neurotransmitter and an important intermediate in the cellular metabolism of the brain, has a widespread influence in the sleep-wake regulatory system. Glutamate transporters, including vesicular glutamate transporters and excitatory amino acid transporters, serve as the main force controlling the extracellular concentration of glutamate in the brain. These are likely to be critical tools needed for the brain to modulate the sleep-wake cycle and are likely innervated by the circadian rhythm system in a day-night variant pattern. Because in the initial stages, nearly all patients with neurodegenerative diseases have rhythmic sleep disorders that become aggravated with disease development and often exhibit glutamate uptake dysfunction, we examined whether the above glutamate transporters could be used as potential targets to help address circadian rhythm sleep disorders in patients with neurodegenerative diseases. Therefore, in this review, we sought to analyze the principles governing glutamate transmission and discuss whether the circadian rhythm regulatory properties of these processes endow glutamate transporters with unique functions in the sleep-wake shift of the brain. We attempt to provide a theoretical framework in this field for future studies, to help in the exploration of potential therapeutic targets to delay or prevent the development of neurodegenerative diseases.