The significant effect of chronic intermittent hypoxia on prostaglandin D2 biosynthesis in rat brain

Obstructive sleep apnea (OSA) is a common disorder characterized by chronic intermittent hypoxia (CIH). Excessive daytime sleepiness (EDS) is one of severe complications frequently associated with OSA. Lipocalin-type prostaglandin synthase (L-PGDS) is potentially responsible for the production of prostaglandin D2 (PGD2) which is an endogenous sleep inducer. To date, whether the content of PGD2 and PGDS is related to intermittent hypoxia has never been reported. The aim of this study was to compare the content of PGD2 and L-PGDS in rats' brains with and without intermittent hypoxia. Adult male Wistar rats (n = 48; 8-10 weeks) were averagely divided into two groups. One was control group, and the other group was exposed to IH (12 h/day for 6 weeks). In each group there are four time-points including 0, 2, 4 and 6 weeks, and six rats were killed and studied at each time-point. At the end of 0, 2, 4 and 6 weeks, the concentrations of PGD2 in brains were measured by LC-MS/MS. In addition, the expressions of L-PGDS protein and mRNA in brains were investigated by western blotting and real-time polymerase chain reaction (RT-PCR), respectively. The results showed the concentrations of PGD2 in CIH rat brains were higher than those in control groups from the second week. At the end of 6 weeks, the concentrations of PGD2 in CIH and control groups were 11.1 and 5.9 ng/g, respectively. The levels of L-PGDS protein and mRNA followed the same trend during the whole 6 weeks. The results will provide a new idea to explore that patients with OSA are always accompanied by excessive daytime sleepiness.