＜Special Seminar＞Molecular mechanism of sleep-wake regulation

概要

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Prostaglandin（ PG） D2 is the most potent endogenous sleep-promoting substance thus far reported and itssleep-inducing mechanism is the best characterized at the molecular level. PGD2 is produced by lipocalin-type PGDsynthase （L-PGDS） localized in the leptomeninges, choroid plexus, and oligodendrocytes in the brain and is secretedinto the cerebrospinal fl uid as a sleep hormone. PGD2 stimulates DP1 receptors localized in the arachnoid membraneat the basal forebrain to release adenosine as a paracrine sleep-promoting molecule, which activates adenosine A2Areceptor-expressing neurons located in the basal forebrain. These cells subsequently excite the sleep-active neuronsin the ventrolateral preoptic area and concomitantly suppress the tuberomammillary nucleus, a histaminergic arousalcenter, through GABAergic and galaninergic inhibitory projection, to induce sleep. The administration of a PGDsynthase inhibitor （SeCl4）, DP1 antagonist （ONO-4127Na） or adenosine A2 receptor antagonist （caffeine） inducesinsomnia, indicating that the PGD2-adenosine system is crucial for the maintenance of physiological sleep.