＜Special Seminar＞Molecular mechanism of sleep-wake regulation

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  • Molecular mechanism of sleep wake regulation

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Prostaglandin（ PG） D2 is the most potent endogenous sleep-promoting substance thus far reported and its sleep-inducing mechanism is the best characterized at the molecular level. PGD2 is produced by lipocalin-type PGD synthase （L-PGDS） localized in the leptomeninges, choroid plexus, and oligodendrocytes in the brain and is secreted into the cerebrospinal fluid as a sleep hormone. PGD2 stimulates DP1 receptors localized in the arachnoid membrane at the basal forebrain to release adenosine as a paracrine sleep-promoting molecule, which activates adenosine A2A receptor-expressing neurons located in the basal forebrain. These cells subsequently excite the sleep-active neurons in the ventrolateral preoptic area and concomitantly suppress the tuberomammillary nucleus, a histaminergic arousal center, through GABAergic and galaninergic inhibitory projection, to induce sleep. The administration of a PGD synthase inhibitor （SeCl4）, DP1 antagonist （ONO-4127Na） or adenosine A2 receptor antagonist （caffeine） induces insomnia, indicating that the PGD2-adenosine system is crucial for the maintenance of physiological sleep.

弘前医学. 61(Suppl.), 2010, p.S164-S173

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  • 弘前医学

    弘前医学 61 (Supplement), S164-S173, 2010-07-08

    弘前大学大学院医学研究科・弘前医学会

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