[Endogenous sleep-promoting substance]

Abstract

Prostaglandin (PG) D2 is the endogenous somnogen that accumulates in the brain during prolonged wakefulness. PGD2 is produced by lipocalin-type PGD synthase localized in the leptomeninges, choroid plexus and oligodendrocytes, and circulates in the cerebrospinal fluid as a sleep hormone. PGD2 stimulates DP1 receptors and increases the local extracellular concentration of adenosine in the basal forebrain as a paracrine sleep-promoting molecule. Adenosine activates sleep-active neurons in the ventrolateral preoptic area (VLPO) through adenosine A2A receptors. Sleep-promoting neurons in the VLPO send inhibitory signals to suppress the histaminergic neurons in the tuberomammillary nucleus, which contribute to arousal through histamine H1 receptors. The neural network between VLPO and TMN is considered to play a key role in the regulation of sleep.