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The Journal of Neuroscience, July 1, 2002, 22(13):5679-5686

Prostaglandin D Synthase in the Prenatal Ovine Brain and Effects of Its Inhibition with Selenium Chloride on Fetal Sleep/Wake Activity In Utero

Brenda Lee, Jonathan J. Hirst, and David W. Walker

Department of Physiology, Monash University, Clayton, Melbourne, Victoria, Australia, 3800

It has been proposed that prostaglandin (PG) D₂ 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 ~125 d gestation (term is ~147 d). In adult animals, PGD synthase (PGDS) (functionally and structurally homologous to -trace protein) is secreted into CSF with a circadian pattern, with the highest concentrations present during sleep. In this study we show that PGDS/-trace protein is present in fetal sheep CSF at 125 and 135 d gestation but not at 90 d gestation. SeCl₄, 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). SeCl₄ at 25 and 1000 pmol/min had no significant effect on arousal activity. Infusion of PGD₂ 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 PGD₂ was infused immediately after a 4 hr infusion of SeCl₄ (500 pmol/min), the SeCl₄-induced increase in arousal behavior was abolished. Together, the presence of PGDS/-trace protein in fetal CSF in late gestation and the effects of SeCl₄ in increasing the incidence of arousal-like behavior suggest that PGD₂ has a role in the induction and maintenance of prenatal sleep.

Key words: fetus; sleep/wake; arousal; prostaglandin D synthase; -trace protein; selenium chloride

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Copyright © 2002 Society for Neuroscience  0270-6474/02/22135679-08$05.00/0

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