Feil Robert, Hölter Sabine M, Weindl Karin, Wurst Wolfgang, Langmesser Sonja, Gerling Andrea, Feil Susanne, Albrecht Urs
Interfakultäres Institut für Biochemie; Universität Tübingen; Tübingen, Germany.
Commun Integr Biol. 2009 Jul;2(4):298-301. doi: 10.4161/cib.2.4.8220.
The second messenger cGMP controls cardiovascular and gastrointestinal homeostasis in mammals. However, its physiological relevance in the nervous system is poorly understood.1 Now, we have reported that the cGMP-dependent protein kinase type I (PRKG1) is implicated in the regulation of the timing and quality of sleep and wakefulness.2Prkg1 mutant mice showed altered distribution of sleep and wakefulness as well as reduction in rapid-eye-movement sleep (REMS) duration and in non-REMS consolidation. Furthermore, the ability to sustain waking episodes was compromised. These observations were also reflected in wheel-running and drinking activity. A decrease in electroencephalogram power in the delta frequency range (1-4 Hz) under baseline conditions was observed, which was normalized after sleep deprivation. Together with the finding that circadian clock amplitude is reduced in Prkg1 mutants these results indicate a decrease of the wake-promoting output of the circadian system affecting sleep. Because quality of sleep might affect learning we tested Prkg1 mutants in several learning tasks and find normal spatial learning but impaired object recognition memory in these animals. Our findings indicate that Prkg1 impinges on circadian rhythms, sleep and distinct aspects of learning.
第二信使环磷酸鸟苷（cGMP）调控哺乳动物的心血管和胃肠道稳态。然而，其在神经系统中的生理相关性却鲜为人知。1如今，我们报道了I型环磷酸鸟苷依赖性蛋白激酶（PRKG1）参与调控睡眠和觉醒的时间及质量。2Prkg1突变小鼠表现出睡眠和觉醒分布改变，快速眼动睡眠（REMS）时长及非快速眼动睡眠巩固过程减少。此外，维持清醒状态的能力也受到损害。这些观察结果也反映在转轮和饮水活动中。在基线条件下观察到脑电图在δ频率范围（1 - 4赫兹）的功率下降，睡眠剥夺后恢复正常。结合Prkg1突变体中昼夜节律振幅降低的发现，这些结果表明昼夜节律系统促进觉醒的输出减少，从而影响睡眠。由于睡眠质量可能影响学习，我们在多项学习任务中测试了Prkg1突变体，发现这些动物的空间学习正常，但物体识别记忆受损。我们的研究结果表明，Prkg1影响昼夜节律、睡眠及学习的不同方面。
