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Astrocyte expression of the Drosophila TNF-alpha homologue, Eiger, regulates sleep in flies
- Source :
- PLoS Genetics, Vol 14, Iss 10, p e1007724 (2018), PLoS Genetics
- Publication Year :
- 2018
- Publisher :
- Public Library of Science (PLoS), 2018.
-
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.<br />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.
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 15537404 and 15537390
- Volume :
- 14
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- PLoS Genetics
- Accession number :
- edsair.doi.dedup.....4817a8b0cda33679f2744e3689fd04fa