title: Prostaglandin D synthase in the prenatal ovine brain and effects of its inhibition with selenium chloride on fetal sleep/wake activity in utero.
abstract: It has been proposed that prostaglandin (PG) D(2) induces physiological sleep in mammals by acting on sleep centers located in the anterior hypothalamus. In fetal sheep, definitive rapid-eye-movement and non-rapid-eye-movement sleep states appear at approximately 125 d gestation (term is approximately 147 d). In adult animals, PGD synthase (PGDS) (functionally and structurally homologous to beta-trace protein) is secreted into CSF with a circadian pattern, with the highest concentrations present during sleep. In this study we show that PGDS/beta-trace protein is present in fetal sheep CSF at 125 and 135 d gestation but not at 90 d gestation. SeCl(4), a specific inhibitor of PGDS, was given to unanesthetized fetal sheep (130-140 d gestation) by intracerebroventricular infusion at a dose of 25, 100, 500, or 1000 pmol/min for 4 hr. Artificial CSF was infused in control experiments. Arousal behavior, defined as the presence of nuchal muscle electromyogram activity, electro-ocular activity, and breathing movements during low-amplitude electrocortical activity, increased from 3.8 +/- 1 min/hr to 6.6 +/- 0.5 and 7.0 +/- 0.3 min/hr at doses of 100 and 500 pmol/min, respectively (p < 0.05). SeCl(4) at 25 and 1000 pmol/min had no significant effect on arousal activity. Infusion of PGD(2) at 500 pmol/min intracerebroventricularly for 4 hr decreased the incidence of arousal from 3.8 +/- 0.5 min/hr to 0.7 +/- 0.3 min/hr (p < 0.05). When 500 pmol/min PGD(2) was infused immediately after a 4 hr infusion of SeCl(4) (500 pmol/min), the SeCl(4)-induced increase in arousal behavior was abolished. Together, the presence of PGDS/beta-trace protein in fetal CSF in late gestation and the effects of SeCl(4) in increasing the incidence of arousal-like behavior suggest that PGD(2) has a role in the induction and maintenance of prenatal sleep.
authors.affiliation: Department of Physiology, Monash University, Clayton, Melbourne, Victoria, Australia, 3800.
authors.forename: Brenda
authors.initials: B
authors.lastname: Lee
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Hirst
authors.forename: David W
authors.initials: DW
authors.lastname: Walker
mesh_terms: D000818:Animals; D001143:Arousal; D001921:Brain / Q000196:embryology* / Q000201:enzymology* / Q000502:physiology; D002552:Cerebral Ventricles; D002712:Chlorides / Q000008:administration & dosage / Q000494:pharmacology*; D005314:Embryonic and Fetal Development; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D005333:Fetus / Q000201:enzymology / Q000502:physiology; D006801:Humans; D007263:Infusions, Parenteral; D019746:Intramolecular Oxidoreductases / Q000037:antagonists & inhibitors* / Q000134:cerebrospinal fluid; D007700:Kinetics; D054834:Lipocalins; D011247:Pregnancy; D015230:Prostaglandin D2 / Q000008:administration & dosage / Q000494:pharmacology; D018036:Selenium Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D012756:Sheep; D012890:Sleep / Q000187:drug effects; D014851:Wakefulness / Q000187:drug effects
chemical_list: D002712:Chlorides; D004791:Enzyme Inhibitors; D054834:Lipocalins; D018036:Selenium Compounds; C070974:selenium tetrachloride; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase; D015230:Prostaglandin D2