1. Astrocyte expression of the Drosophila TNF-alpha homologue, Eiger, regulates sleep in flies
- Author
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Jason R. Gerstner, Rebecca H. Taylor, Alan G. Goodman, William M. Vanderheyden, Marcos G. Frank, and Hans P. A. Van Dongen
- Subjects
0301 basic medicine ,Macroglial Cells ,Cancer Research ,Physiology ,Biochemistry ,Receptors, Tumor Necrosis Factor ,RNA interference ,0302 clinical medicine ,Animal Cells ,Immune Physiology ,Medicine and Health Sciences ,Drosophila Proteins ,Genetics (clinical) ,Neurons ,Mammals ,Innate Immune System ,Gene knockdown ,biology ,Drosophila Melanogaster ,Eukaryota ,Animal Models ,Sleep in non-human animals ,Cell biology ,Nucleic acids ,Insects ,medicine.anatomical_structure ,Genetic interference ,Experimental Organism Systems ,Neurology ,Vertebrates ,Cytokines ,Epigenetics ,Drosophila ,Tumor necrosis factor alpha ,Cellular Types ,medicine.symptom ,Drosophila melanogaster ,Signal transduction ,Signal Transduction ,Research Article ,Astrocyte ,Arthropoda ,lcsh:QH426-470 ,Immunology ,Glial Cells ,Research and Analysis Methods ,Evolution, Molecular ,03 medical and health sciences ,Model Organisms ,Genetics ,medicine ,Animals ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,Tumor Necrosis Factor-alpha ,Organisms ,Membrane Proteins ,Biology and Life Sciences ,Cell Biology ,Molecular Development ,biology.organism_classification ,Invertebrates ,Sleep deprivation ,lcsh:Genetics ,030104 developmental biology ,Astrocytes ,Immune System ,Cellular Neuroscience ,Amniotes ,Animal Studies ,RNA ,Sleep Deprivation ,Gene expression ,Sleep ,Physiological Processes ,030217 neurology & neurosurgery ,Developmental Biology ,Neuroscience - Abstract
Sleep contributes to cognitive functioning and is sufficient to alter brain morphology and function. However, mechanisms underlying sleep regulation remain poorly understood. In mammals, tumor necrosis factor-alpha (TNFα) is known to regulate sleep, and cytokine expression may represent an evolutionarily ancient mechanism in sleep regulation. Here we show that the Drosophila TNFα homologue, Eiger, mediates sleep in flies. We show that knockdown of Eiger in astrocytes, but not in neurons, significantly reduces sleep duration, and total loss-of-function reduces the homeostatic response to sleep loss. In addition, we show that neuronal, but not astrocyte, expression of the TNFα receptor superfamily member, Wengen, is necessary for sleep deprivation-induced homeostatic response and for mediating increases in sleep in response to human TNFα. These data identify a novel astrocyte-to-neuron signaling mechanism in the regulation of sleep homeostasis and show that the Drosophila cytokine, Eiger, represents an evolutionarily conserved mechanism of sleep regulation across phylogeny., Author summary Every animal sleeps, from fruit flies to humans. However, the function of sleep is still currently unknown. Identifying conserved mechanisms of sleep regulation in evolutionarily ancient organisms may help us to understand the function of sleep. Therefore, we have examined whether Eiger, the homologue of the cytokine tumor necrosis factor-alpha (TNFα), regulates sleep in the fruit fly as it does in higher mammals. Cytokines are inflammatory molecules and are typically elevated following infection or fever and may contribute to increased sleepiness when sick. We found that, in the fruit fly, Eiger regulates sleep duration just like TNFα does in mammals: increasing cytokine levels increased sleep duration while decreasing Eiger reduced sleep. In addition, we found that Eiger expression in glial astrocytes, is responsible for the alteration in sleep duration. We also examined the necessity of Eiger receptor activation on neurons and found that astrocyte-to-neuron communication was required for regulating the normal increases in sleep following sleep deprivation. These data show that a novel cytokine mechanism regulates sleep in flies and mammals, and provides insight into conserved roles of astrocytes in sleep behavior.
- Published
- 2018