cgmp-dependent protein kinase type i is implicated in the regulation of the timing and quality of sleep and wakefulnesscgmp-dependent蛋白激酶i型监管有牵连的睡眠和清醒的时间和质量.pdfVIP

cGMP-Dependent Protein Kinase Type I Is Implicated in the Regulation of the Timing and Quality of Sleep and Wakefulness 1. 2. 3 2 1 3 Sonja Langmesser , Paul Franken , Susanne Feil , Yann Emmenegger , Urs Albrecht *, Robert Feil 1 Division of Biochemistry, Department of Medicine, University of Fribourg, Fribourg, Switzerland, 2 Center for Integrative Genomics, University of Lausanne, Lausanne, ¨ ¨ ¨ ¨ ¨ Switzerland, 3 Interfakultares Institut fur Biochemie, Universitat Tubingen, Tubingen, Germany Abstract Many effects of nitric oxide (NO) are mediated by the activation of guanylyl cyclases and subsequent production of the second messenger cyclic guanosine-39,5 9-monophosphate (cGMP). cGMP activates cGMP-dependent protein kinases (PRKGs), which can therefore be considered downstream effectors of NO signaling. Since NO is thought to be involved in the regulation of both sleep and circadian rhythms, we analyzed these two processes in mice deficient for cGMP-dependent protein kinase type I (PRKG1) in the brain. Prkg1 mutant mice showed a strikingly altered distribution of sleep and wakefulness over the 24 hours of a day as well as reductions in rapid-eye-movement sleep (REMS) duration and in non-REM sleep (NREMS) consolidation, and their ability to sustain waking episodes was compromised. Furthermore, they displayed a drastic decrease in electroencephalogram (EEG) power in the delta frequency range (1–4 Hz) under baseline conditions, which could be normalized after sleep deprivation. In line with the re-distribution of sleep and wakefulness, the analysis of wheel-r