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 24 h 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. (C) 2011 Elsevier B.V. All rights reserved.