Characteristics of sleep-wake cycles in mice lacking prostanoid DP receptors / 中国临床药理学与治疗学

AIM: To investigate the effect of prostanoid DP receptors (DPR) on sleep-wake regulation in mice. METHODS: Under pentobarbital anesthesia, mice were chronically implanted with electroencephalogram (EEG) and electromyogram (EMG) electrodes for polysomnographic recordings. The spontaneous sleep-wake cycles were monitored continuously by EEG/EMG recording system for 24 h beginning at 800 p.m. and analyzed by SLEEPSIGN software in DPR knock out (KO) and wild type (WT) mice. RESULTS: DPR-KO mice exhibited a similar circadian rhythm of sleep-wake cycles to WT mice. The amounts of rapid eye movement (REM) sleep or non-REM (NREM) sleep during both the light and dark periods were identical between the DPR-KO and WT mice. Whereas, an increase in the episode number of wakefulness and a shortage in the duration of NREM sleep were found in DPR-KO mice during the light period compared with WT mice. Moreover, DPR-KO mice showed lower activity in delta-wave component in NREM sleep and higher activity in theta-wave component in REM sleep than WT mice. CONCLUSION: DPR plays a crucial role in mediating the prostaglandin D2-induced sleep. Deficiency of DPR results in the low intensity and fragmented diurnal NREM sleep and the high vigilance REM sleep, with the normal circadian rhythm of sleep in mice.

Effect of prostaglandin D_2 on sleep regulation / 中国临床药理学与治疗学

Prostaglandin (PG) D_2 is one of unsaturated fatty acids with 20 carbon atoms, which is synthesized by PGD synthase (PGDS) in the brain. PGD_2 has been identified to be a sleep-inducing substance that becomes bound to the DP receptor (DPR) exclusively localized on the surface of the basal forebrain, leading to an increase in extracellular adenosine levels there. Through A_ 2A receptors (A_ 2A R), the adenosine activates neurons in the ventrolateral preoptic area (VLPO), a putative sleep center, and inhibits neurons in the histaminergic tuberomammillary nucleus (TMN), a putative wake center, via GABA to induce sleep. Studying the effect and the molecular mechanisms of sleep-induced by PGD_2 would be helpful in the development of novel sleeping drugs for more rational treatment of sleep disorders.