title: Cellular stress induces a protective sleep-like state in C. elegans.
abstract: 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.
authors.affiliation: Department of Biology, California State University, Northridge, Northridge, CA 91330, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Hill
authors.affiliation: Department of Biology, California State University, Northridge, Northridge, CA 91330, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Mansfield
authors.affiliation: Department of Biology, California State University, Northridge, Northridge, CA 91330, USA.
authors.forename: Jessie M N G
authors.initials: JM
authors.lastname: Lopez
authors.affiliation: Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Raizen
authors.affiliation: Department of Biology, California State University, Northridge, Northridge, CA 91330, USA. Electronic address: cheryl.vanbuskirk@csun.edu.
authors.forename: Cheryl
authors.initials: C
authors.lastname: Van Buskirk
mesh_terms: D000818:Animals; D000083722:Bacillus thuringiensis Toxins; D001426:Bacterial Proteins / Q000633:toxicity; D017173:Caenorhabditis elegans / Q000502:physiology*; D003080:Cold Temperature; D004731:Endotoxins / Q000633:toxicity; D000431:Ethanol / Q000633:toxicity; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006460:Hemolysin Proteins / Q000633:toxicity; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology; D006358:Hot Temperature; D012890:Sleep / Q000502:physiology*; D013312:Stress, Physiological / Q000187:drug effects / Q000502:physiology*
chemical_list: D000083722:Bacillus thuringiensis Toxins; D001426:Bacterial Proteins; D004731:Endotoxins; D006460:Hemolysin Proteins; C030956:insecticidal crystal protein, Bacillus Thuringiensis; D000431:Ethanol