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.
Highlights
The function of sleep and the neurobiology underlying the detrimental effects of sleep deprivation on physiological function are poorly understood
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
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
Summary
The function of sleep and the neurobiology underlying the detrimental effects of sleep deprivation on physiological function are poorly understood. In the fruit fly Drosophila melanogaster, molecules involved in inflammation and immunological functioning have been implicated in sleep regulation including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) [7] and Jun amino-terminal kinases (JNK) [8]. In mammals, another such molecule is the pro-inflammatory cytokine, tumor necrosis factor alpha (TNFα). Given the importance TNFα signaling for sleep in mammals and the role of inflammation and immunological genes in sleep regulation in the fly, we examined the Drosophila melanogaster TNFα homologue, Eiger, to determine evolutionarily conserved mechanisms of cytokines in sleep
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