cGMP-dependent protein kinase type I is implicated in the regulation of the timing and quality of sleep and wakefulness.
cGMP-dependent protein kinase type I is implicated in the regulation of the timing and quality of sleep and wakefulness.
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DOI：
10.1371/journal.pone.0004238
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发表时间：
2009
期刊：
影响因子：
3.7
通讯作者：
Feil R
中科院分区：
文献类型：
--
作者：
Langmesser S;Franken P;Feil S;Emmenegger Y;Albrecht U;Feil R
一氧化氮（NO）的许多作用是通过鸟苷环化酶的激活和随后产生的第二信使环鸟苷-3′，5′-单磷酸（cGMP）介导的。cGMP激活cGMP依赖性蛋白激酶（PRKGs），因此可以认为是NO信号的下游效应器。由于NO被认为参与睡眠和昼夜节律的调节，我们在大脑中缺乏cgmp依赖性蛋白激酶I型（PRKG1）的小鼠中分析了这两个过程。Prkg1突变小鼠在一天24小时内的睡眠和清醒分布发生了显著变化，快速眼动睡眠（REMS）持续时间和非快速眼动睡眠（NREMS）巩固时间也有所减少，它们维持清醒发作的能力也受到了损害。此外，在基线条件下，他们在δ频率范围（1-4 Hz）的脑电图（EEG）功率急剧下降，这在睡眠剥夺后可以正常化。与睡眠和清醒的重新分布一致，对轮子跑步和饮酒活动的分析显示，突变动物在活动阶段有更多的休息时间，白天活动的比例更高。生物钟的内部周期长度和相移特性没有变化，但卡方周期图幅度明显减小，暗示振荡器的鲁棒性较差。这些结果表明，PRKG1可能参与了小鼠昼夜节律振荡器的稳定和输出强度。此外，PRKG1缺乏会导致异常模式，从而导致睡眠和觉醒质量下降，这可能是由于影响睡眠的昼夜节律系统促进觉醒的输出减少所致。
Many effects of nitric oxide (NO) are mediated by the activation of guanylyl cyclases and subsequent production of the second messenger cyclic guanosine-3′,5′-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-running and drinking activity revealed more rest bouts during the activity phase and a higher percentage of daytime activity in mutant animals. No changes were observed in internal period length and phase-shifting properties of the circadian clock while chi-squared periodogram amplitude was significantly reduced, hinting at a less robust oscillator. These results indicate that PRKG1 might be involved in the stabilization and output strength of the circadian oscillator in mice. Moreover, PRKG1 deficiency results in an aberrant pattern, and consequently a reduced quality, of sleep and wakefulness, possibly due to a decreased wake-promoting output of the circadian system impinging upon sleep.
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DOI：
10.1152/ajpregu.2001.280.5.r1348
发表时间：
2001-05-01
影响因子：
2.8
作者：
Ferreyra, GA;Golombek, DA
通讯作者：
Golombek, DA
影响因子：
3.3
作者：
Burlet, S;Leger, L;Cespuglio, R
通讯作者：
Cespuglio, R
DOI：
10.1073/pnas.0602006103
发表时间：
2006-05-02
影响因子：
11.1
作者：
Franken, P;Dudley, CA;McKnight, SL
通讯作者：
McKnight, SL
DOI：
10.1073/pnas.93.20.10887
发表时间：
1996-10-01
影响因子：
11.1
作者：
Feil, R;Brocard, J;Chambon, P
通讯作者：
Chambon, P
DOI：
10.1152/ajpregu.1998.275.4.r1127
发表时间：
1998-10-01
影响因子：
2.8
作者：
Franken, P;Malafosse, A;Tafti, M
通讯作者：
Tafti, M