Hill Andrew J, Mansfield Richard, Lopez Jessie M N G, Raizen David M, Van Buskirk Cheryl
Department of Biology, California State University, Northridge, Northridge, CA 91330, USA.
Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
Curr Biol. 2014 Oct 20;24(20):2399-405. doi: 10.1016/j.cub.2014.08.040. Epub 2014 Sep 25.
Sleep is recognized to be ancient in origin, with vertebrates and invertebrates experiencing behaviorally quiescent states that are regulated by conserved genetic mechanisms. Despite its conservation throughout phylogeny, the function of sleep remains debated. Hypotheses for the purpose of sleep include nervous-system-specific functions such as modulation of synaptic strength and clearance of metabolites from the brain, as well as more generalized cellular functions such as energy conservation and macromolecule biosynthesis. These models are supported by the identification of synaptic and metabolic processes that are perturbed during prolonged wakefulness. It remains to be seen whether perturbations of cellular homeostasis in turn drive sleep. Here we show that under conditions of cellular stress, including noxious heat, cold, hypertonicity, and tissue damage, the nematode Caenorhabditis elegans engages a behavioral quiescence program. The stress-induced quiescent state displays properties of sleep and is dependent on the ALA neuron, which mediates the conserved soporific effect of epidermal growth factor (EGF) ligand overexpression. We characterize heat-induced quiescence in detail and show that it is indeed dependent on components of EGF signaling, providing physiological relevance to the behavioral effects of EGF family ligands. We find that after noxious heat exposure, quiescence-defective animals show elevated expression of cellular stress reporter genes and are impaired for survival, demonstrating the benefit of stress-induced behavioral quiescence. These data provide evidence that cellular stress can induce a protective sleep-like state in C. elegans and suggest that a deeply conserved function of sleep is to mitigate disruptions of cellular homeostasis.
睡眠被认为起源古老，脊椎动物和无脊椎动物都会经历由保守的遗传机制调节的行为静止状态。尽管睡眠在整个系统发育过程中都得以保留，但其功能仍存在争议。关于睡眠目的的假说包括神经系统特有的功能，如调节突触强度和清除大脑中的代谢物，以及更普遍的细胞功能，如能量守恒和大分子生物合成。这些模型得到了在长时间清醒期间受到干扰的突触和代谢过程的识别的支持。细胞内稳态的扰动是否反过来驱动睡眠还有待观察。在这里，我们表明，在细胞应激条件下，包括有害热、冷、高渗和组织损伤，线虫秀丽隐杆线虫会启动行为静止程序。应激诱导的静止状态表现出睡眠的特性，并依赖于ALA神经元，该神经元介导表皮生长因子（EGF）配体过表达的保守催眠作用。我们详细描述了热诱导的静止状态，并表明它确实依赖于EGF信号通路的组成部分，为EGF家族配体的行为效应提供了生理相关性。我们发现，在受到有害热暴露后，静止缺陷的动物细胞应激报告基因的表达升高，并且生存能力受损，这表明应激诱导的行为静止具有益处。这些数据提供了证据，证明细胞应激可以在秀丽隐杆线虫中诱导一种保护性的类似睡眠的状态，并表明睡眠的一个深度保守功能是减轻细胞内稳态的破坏。
