＜Special Seminar＞Molecular mechanism of sleep-wake regulation
Year: 2010
Type: article
Abstract: Prostaglandin（ PG） D2 is the most potent endogenous sleep-promoting substance thus far reported and its\nsleep-inducing mechanism is the best characterized at the molecular level. PGD2 is produced by lipocalin-type PGD\nsynthase （L-PGDS） localized in the leptomeninges, choroid plexus, and oligodendrocytes in the brain and is secreted\ninto the cerebrospinal fl uid as a sleep hormone. PGD2 stimulates DP1 receptors localized in the arachnoid membrane\nat the basal forebrain to release adenosine as a paracrine sleep-promoting molecule, which activates adenosine A2A\nreceptor-expressing neurons located in the basal forebrain. These cells subsequently excite the sleep-active neurons\nin the ventrolateral preoptic area and concomitantly suppress the tuberomammillary nucleus, a histaminergic arousal\ncenter, through GABAergic and galaninergic inhibitory projection, to induce sleep. The administration of a PGD\nsynthase inhibitor （SeCl4）, DP1 antagonist （ONO-4127Na） or adenosine A2 receptor antagonist （caffeine） induces\ninsomnia, indicating that the PGD2-adenosine system is crucial for the maintenance of physiological sleep.
Author: Yoshihiro Urade
Language: Japanese
Subfield: Cognitive Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2735607841