PT - JOURNAL ARTICLE AU - Brenda Lee AU - Jonathan J. Hirst AU - David W. Walker TI - Prostaglandin D Synthase in the Prenatal Ovine Brain and Effects of Its Inhibition with Selenium Chloride on Fetal Sleep/Wake Activity<em>In Utero</em> AID - 10.1523/JNEUROSCI.22-13-05679.2002 DP - 2002 Jul 01 TA - The Journal of Neuroscience PG - 5679--5686 VI - 22 IP - 13 4099 - http://www.jneurosci.org/content/22/13/5679.short 4100 - http://www.jneurosci.org/content/22/13/5679.full SO - J. Neurosci.2002 Jul 01; 22 AB - 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 β-trace protein) is secreted into CSF with a circadian pattern, with the highest concentrations present during sleep. In this study we show that PGDS/β-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 &lt; 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 &lt; 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/β-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.