Prostaglandin (PG)s D
2 and E
2 are the major arachidonic acid metabolites in the mammalian brain. PGD synthase, the enzyme that produces PGD
2 in the brain, is mainly localized in the arachnoid membrane and choroid plexus. It is secreted into the cerebrospinal fluid and circulates in the brain through the ventricular system. PGD
2 induces sleep by acting on the surface of the ventro-medial region of the rostral basal forebrain, the signal of which is probably transmitted into the brain parenchyma by adenosine via adenosine A
2a receptors. Fos expression experiments suggest that PGD
2 inhibits histaminergic arousal neurons of the tuberomammillary nucleus (TMN) in the posterior hypothalamus by activating inhibitory neurons in the ventrolateral preoptic area (VLPO). However, PGE
2 causes wakefulness by activating arousal neurons in the TMN via AMPA type excitatory amino acid receptors. Therefore, PGD
2, acting as a sleep-inducer, and PGE
2, acting as a wakefulness-promoter, jointly regulate the generation of sleep and wakefulness in the mammalian brain.
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