Alcohol induces long-lasting sleep deficits in Drosophila via subsets of cholinergic neurons.

IF 8.1 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Current Biology Pub Date : 2025-03-10 Epub Date: 2025-02-06 DOI:10.1016/j.cub.2025.01.026
Maggie M Chvilicek, Iris Titos, Collin B Merrill, Pearl N Cummins-Beebee, Justin D Chen, Aylin R Rodan, Adrian Rothenfluh
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引用次数: 0

Abstract

Alcohol consumption causes short- and long-term sleep impairments, which persist into recovery from alcohol use disorder (AUD). In humans, sleep quantity and quality are disturbed even after 2 weeks of alcohol abstinence in as many as 72% of AUD patients. These sleep deficits are strong predictors of relapse to drinking, but their underlying biological mechanisms are poorly understood, making them difficult to treat in a targeted manner. Here, we took advantage of Drosophila melanogaster's translational relevance for human sleep and alcohol responses to model human alcohol-induced sleep deficits and determine mechanisms of these effects. While low doses of alcohol stimulate the central nervous system (CNS) in flies and in humans, high doses depress the CNS, leading to sedation. After a single, sedating alcohol exposure, flies experienced loss of nighttime sleep, increased time to fall asleep, and reduced sleep quality. These effects lasted for days but eventually recovered. Hyperactivating ethanol exposures failed to induce sleep deficits, even when repeated, suggesting that CNS-depressant effects of sedating ethanol exposures are required for long-lasting sleep deficits. By manipulating activity in neurons producing different neurotransmitters, we determined that reduced cholinergic activity synergized with a sub-sedating ethanol exposure to cause sleep deficits. We then identified subsets of cholinergic neurons mediating these effects, which included mushroom body neurons previously implicated in sleep and alcohol responses. When those neurons were excluded, sleep effects were abrogated. These data suggest that ethanol-induced suppression of cholinergic neurons induces long-lasting sleep deficits, which are conserved from Drosophila to humans.

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来源期刊
Current Biology
Current Biology 生物-生化与分子生物学
CiteScore
11.80
自引率
2.20%
发文量
869
审稿时长
46 days
期刊介绍: Current Biology is a comprehensive journal that showcases original research in various disciplines of biology. It provides a platform for scientists to disseminate their groundbreaking findings and promotes interdisciplinary communication. The journal publishes articles of general interest, encompassing diverse fields of biology. Moreover, it offers accessible editorial pieces that are specifically designed to enlighten non-specialist readers.
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