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Titolo:
Molecular mechanisms of sleep-wake regulation: a role of prostaglandin D-2
Autore:
Hayaishi, O;
Indirizzi:
Osaka Biosci Inst, Suita, Osaka 5650874, Japan Osaka Biosci Inst Suita Osaka Japan 5650874 , Suita, Osaka 5650874, Japan
Titolo Testata:
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY OF LONDON SERIES B-BIOLOGICAL SCIENCES
fascicolo: 1394, volume: 355, anno: 2000,
pagine: 275 - 280
SICI:
0962-8436(20000229)355:1394<275:MMOSRA>2.0.ZU;2-4
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN CEREBROSPINAL-FLUID; BETA-TRACE PROTEIN; D SYNTHASE; RAT-BRAIN; MESSENGER-RNA; CHOROID-PLEXUS; D RECEPTOR; EXPRESSION; IDENTIFICATION; LEPTOMENINGES;
Keywords:
prostaglandin D-2; sleep; PGD synthase; adenosine; Fos;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Agriculture,Biology & Environmental Sciences
Life Sciences
Citazioni:
28
Recensione:
Indirizzi per estratti:
Indirizzo: Hayaishi, O Osaka Biosci Inst, 6-2-4 Furuedai, Suita, Osaka 5650874, JapanOsaka Biosci Inst 6-2-4 Furuedai Suita Osaka Japan 5650874 pan
Citazione:
O. Hayaishi, "Molecular mechanisms of sleep-wake regulation: a role of prostaglandin D-2", PHI T ROY B, 355(1394), 2000, pp. 275-280

Abstract

Prostaglandin (PG) D-2 is a major prostanoid in the brains of rats and other mammals, including humans. When PGD synthase (PGDS), the enzyme that produces PGD(2) in the brain, was inhibited by the intracerebroventricular infusion of its selective inhibitors, i.e. tetravalent selenium compounds, theamount of sleep decreased both time and dose dependently. The amount of sleep of transgenic mice, in which the human PGDS gene had been incorporated,increased several fold under appropriate conditions. These data indicate that PGDS is a key enzyme in sleep regulation. In situ hybridization, immunoperoxidase staining and direct enzyme activity determination of tissue samples revealed that PGDS is hardly delectable in the brain parenchyma but is localized in the membrane systems surrounding the brain, namely, the arachnoid membrane and choroid plexus, from which it is secreted into the cerebrospinal fluid (CSF) to become beta-trace, a major protein component of the CSF. PGD(2) exerts its somnogenic activity by binding to PGD(2) receptors exclusively localized at the ventrorostral surface of the basal forebrain. When PGD(2) was infused into the subarachnoid space below the rostral basal forebrain, striking expression of proto-oncogene Fos immunoreactivity (FosIR) was observed in the ventrolateral preoptic area (VLPO), a putative sleep centre, concurrent with sleep induction. Fos expression in the VLPO was positively correlated with the preceding amount of sleep and negatively correlated with Fos expression in the tuberomammillary nucleus (TMN), a putative wake centre. These observations suggest that PGD(2) may induce sleep via leptomeningeal PGD(2) receptors with subsequent activation of the VLPO neurons and downregulation of the wake neurons in the TMN area. Adenosine may be involved in the signal transduction associated with PGD(2).

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/04/20 alle ore 02:25:24