Prostaglandin E2 produced by microsomal prostaglandin E synthase-1 regulates the onset and the maintenance of wakefulness.

This study examined the effect of prostaglandin E(2) (PGE(2)) produced by microsomal prostaglandin E synthase-1 (mPGES-1) on circadian rhythm. Using wild-type mice (WT) and mPGES-1 knockout mice (mPGES-1(-/-)), I recorded and automatically analyzed the natural behavior of mice in home cages for 24h and measured brain levels of PGE(2). The switch to wakefulness was not smooth, and sleepiness and the total duration of sleep were significantly longer in the mPGES-1(-/-) mice. Moreover, the basal concentration of PGE(2) was significantly lower in the mPGES-1(-/-) mice. These findings suggest that PGE(2) produced by mPGES-1 regulates the onset of wakefulness and the maintenance of circadian rhythm.