Chair of Cellular Circuits and Systems, Biotechnology Center (BIOTEC), Center for Molecular and Cellular Bioengineering (CMCB), Technical University Dresden, 01307 Dresden, Germany.
Bioanalytical Mass Spectrometry Group, Max Planck Institute for Multidisciplinary Sciences, 37077 Göttingen, Germany.
Curr Biol. 2022 May 23;32(10):2248-2262.e9. doi: 10.1016/j.cub.2022.04.012. Epub 2022 May 2.
Sleep is an essential state that allows for recuperation and survival processes. Disturbing sleep triggers stress responses that promote protective gene expression. Sleep and its deprivation grossly impact gene expression, but little is known about how normal or disturbed sleep control gene expression. Central to the induction of sleep are sleep-active neurons, which inhibit wakefulness and promote survival. Sleep and sleep-active neurons are highly conserved. In Caenorhabditis elegans, the sleep-active RIS neuron is crucial for sleep and survival. Here, we show that RIS depolarization promotes the protective gene expression response that occurs during developmental arrest. This response includes the activation of FOXO/DAF-16 and expression of DAF-16 target genes such as HSP-12.6, a small heat-shock protein that is required for starvation survival. Disturbing sleep by mechanical stimulation increases RIS depolarization. RIS activation in turn activates DAF-16 and other genes required for survival. Hence, during normal sleep, RIS depolarization promotes protective gene expression. When sleep is disturbed, protective gene expression gets further increased by raised RIS depolarization. We thus link sleep-active neuron depolarization to protective gene expression changes and suggest that the cellular stress response following sleep deprivation could be understood as a safeguarding process that is caused by the overactivation of sleep-active neurons.
睡眠是一种基本状态，有助于恢复和生存过程。睡眠受到干扰会引发应激反应，促进保护性基因表达。睡眠及其剥夺会严重影响基因表达，但对于正常或紊乱的睡眠如何控制基因表达知之甚少。诱导睡眠的核心是睡眠活跃神经元，它抑制觉醒并促进生存。睡眠和睡眠活跃神经元高度保守。在秀丽隐杆线虫中，睡眠活跃的 RIS 神经元对于睡眠和生存至关重要。在这里，我们表明 RIS 的去极化促进了发育停滞期间发生的保护性基因表达反应。这种反应包括 FOXO/DAF-16 的激活和 DAF-16 靶基因的表达，如 HSP-12.6，这是一种小热休克蛋白，对于饥饿生存是必需的。通过机械刺激扰乱睡眠会增加 RIS 的去极化。反过来，RIS 的激活又会激活 DAF-16 和其他生存所需的基因。因此，在正常睡眠期间，RIS 的去极化促进了保护性基因的表达。当睡眠受到干扰时，RIS 去极化的增加进一步增加了保护性基因的表达。因此，我们将睡眠活跃神经元的去极化与保护性基因表达的变化联系起来，并提出睡眠剥夺后的细胞应激反应可以被理解为睡眠活跃神经元过度激活引起的保护过程。
