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

Abstract

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 sleep͞wake patterns between wild-type and TG 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 TG mice after stimulation by tail clipping. Concomitantly, the spontaneous locomotor activity of TG animals was drastically decreased in response to the tail clip. Induction of NREM sleep in TG mice was positively correlated with the PGD2 production in the brain. Sleep, locomotion, and PGD2 content were essentially unchanged in wild-type mice after tail clipping. The results with TG mice demonstrate the involvement of the PGDS gene in the regulation of NREM sleep.

Perchance to dream: Solving the mystery of sleep through genetic analysis

“…These data suggest that the arousing effects of orexin A are mediated by the H1R. Similarly, prostaglandin D2 is a powerful sleep promoting substance that, when over expressed, does not change the amount of timing of NREM and REM sleep (Pinzar et al, 2000). However, transgenic animals [B7 and B20, Fig.…”

Augmented generation of protein fragments during wakefulness as the molecular cause of sleep: a hypothesis

“…4,16,29,31,36,[67][68][69][70][71][72][73][74][75][76][77][78][79] Another potent endogenous somnogen is the PGD 2 prostaglandin, which preferentially induces NREM sleep. 11,28,80,81 The somnogenic activity of PGD 2 is mediated at least in part by the ability of brain-produced PGD 2 to increase the concentration of extracellular adenosine. 11,28,81 Small compounds such as adenosine, ATP, and PGD 2 , proteins such as inflammatory cytokines, and several other endogenous effectors that act as Varshavsky somnogens are a part of the growing understanding of specific circuits that initiate, maintain, and regulate sleep.…”

“…11,28,80,81 The somnogenic activity of PGD 2 is mediated at least in part by the ability of brain-produced PGD 2 to increase the concentration of extracellular adenosine. 11,28,81 Small compounds such as adenosine, ATP, and PGD 2 , proteins such as inflammatory cytokines, and several other endogenous effectors that act as Varshavsky somnogens are a part of the growing understanding of specific circuits that initiate, maintain, and regulate sleep. However, none of this understanding addresses, by itself, the underlying molecular cause and molecular-level function of sleep, which remain unknown.…”

Pivotal roles of the parasite PGD2 synthase and of the host D prostanoid receptor 1 in schistosome immune evasion

“…PGD 2 is generated from the cyclooxygenase product PGH 2 through the action of PGD 2 synthases (PGDS) [16]. In mammals, two genetically distinct forms of PGDS have been identified: the lipocalin-type PGDS, localized in the central nervous system, ocular tissues and genital organs [17,18], and the hematopoietic-type, glutathione (GSH)-dependent, PGDS (H-PGDS), widely distributed in peripheral tissues, APC, mast cells and megakaryocytes [19][20][21]. To date, PGDS from parasites have not been molecularly identified.…”