Neurofibromin 1 mediates sleep depth in Drosophila

Elizabeth B Brown; Jiwei Zhang; Evan Lloyd; Elizabeth Lanzon; Valentina Botero; Seth Tomchik; Alex C Keene

doi:10.1371/journal.pgen.1011049

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Neurofibromin 1 mediates sleep depth in Drosophila

Journal article

Open access

Peer reviewed

Neurofibromin 1 mediates sleep depth in Drosophila

Elizabeth B Brown, Jiwei Zhang, Evan Lloyd, Elizabeth Lanzon, Valentina Botero, Seth Tomchik and Alex C Keene

PLoS genetics, Vol.19(12), e1011049

12/13/2023

DOI: 10.1371/journal.pgen.1011049

PMCID: PMC10763969

PMID: 38091360

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Abstract

Neural regulation of sleep and metabolic homeostasis are critical in many aspects of human health. Despite extensive epidemiological evidence linking sleep dysregulation with obesity, diabetes, and metabolic syndrome, little is known about the neural and molecular basis for the integration of sleep and metabolic function. The RAS GTPase-activating gene Neurofibromin (Nf1) has been implicated in the regulation of sleep and metabolic rate, raising the possibility that it serves to integrate these processes, but the effects on sleep consolidation and physiology remain poorly understood. A key hallmark of sleep depth in mammals and flies is a reduction in metabolic rate during sleep. Here, we examine multiple measures of sleep quality to determine the effects of Nf1 on sleep-dependent changes in arousal threshold and metabolic rate. Flies lacking Nf1 fail to suppress metabolic rate during sleep, raising the possibility that loss of Nf1 prevents flies from integrating sleep and metabolic state. Sleep of Nf1 mutant flies is fragmented with a reduced arousal threshold in Nf1 mutants, suggesting Nf1 flies fail to enter deep sleep. The effects of Nf1 on sleep can be localized to a subset of neurons expressing the GABAA receptor Rdl. Sleep loss has been associated with changes in gut homeostasis in flies and mammals. Selective knockdown of Nf1 in Rdl-expressing neurons within the nervous system increases gut permeability and reactive oxygen species (ROS) in the gut, raising the possibility that loss of sleep quality contributes to gut dysregulation. Together, these findings suggest Nf1 acts in GABA-sensitive neurons to modulate sleep depth in Drosophila.

Details

Title: Subtitle: Neurofibromin 1 mediates sleep depth in Drosophila
Creators: Elizabeth B Brown - Department of Biological Sciences, Florida State University, Tallahassee, Florida, United States of America
Jiwei Zhang - Department of Biology, Texas A&M University, College Station, Texas, United States of America
Evan Lloyd - Department of Biology, Texas A&M University, College Station, Texas, United States of America
Elizabeth Lanzon - Florida Atlantic University
Valentina Botero - University of Iowa
Seth Tomchik - University of Iowa
Alex C Keene - Department of Biology, Texas A&M University, College Station, Texas, United States of America
Resource Type: Journal article
Publication Details: PLoS genetics, Vol.19(12), e1011049
DOI: 10.1371/journal.pgen.1011049
PMID: 38091360
PMCID: PMC10763969
NLM abbreviation: PLoS Genet
eISSN: 1553-7404
Grant note: name: National Institute of Health, award: R21NS124198; name: National Institute of Health, award: R01DC017390; name: National Institute of Health, award: R01 NS126361, R01 NS114403, R01 NS097237; name: National Institute of Health, award: K99AG071833
Language: English
Date published: 12/13/2023
Academic Unit: Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Neuroscience and Pharmacology
Record Identifier: 9984530278402771

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