Prostaglandin D synthase gene is involved in the regulation of non-rapid eye movement sleep

To examine the function of prostaglandin (PG) D synthase (PGDS) gene, as well as endogenously produced PGD(2) in sleep regulation in vivo, we generated transgenic (TG) mice that overexpress human PGDS gene to study their sleep behavior. Although no difference was observed in the sleep/wake patterns between wild-type and To mice, a striking time-dependent increase in non-rapid eye movement (NREM). but not in rapid eye movement (REM), sleep was observed in two independent lines of To mice after stimulation by tail clipping. Concomitantly, the spontaneous locomotor activity of To animals was drastically decreased in response to the tail clip. Induction of NREM sleep in To mice was positively correlated with the PGD2 production in the brain. Sleep, locomotion, and PGD(2) content were essentially unchanged in wild-type mice after tail clipping. The results with To mice demonstrate the involvement of the PGDS gene in the regulation of NREM sleep.