Sleep modulates alcohol toxicity in Drosophila

AbstractStudy ObjectivesAlcohol abuse is a significant public health problem, particularly in populations in which sleep deprivation is common as such as shift workers and aged individuals. Although research demonstrates the effect of alcohol on sleep, little is known about the role of sleep in alcohol sensitivity and toxicity. We investigated sleep as a factor modulating alcohol toxicity using Drosophila melanogaster, a model system ideal for studies of sleep, alcohol and aging.MethodsFollowing 24 hours of sleep deprivation using mechanical stimulation, Drosophila were exposed to binge-like alcohol exposures. Behavioral sensitivity, tolerance, and mortality were assessed. The effects of chronic sleep deprivation on alcohol toxicity were investigated using a short sleep mutant insomniac. Pharmacological induction of sleep for prior to alcohol exposure was accomplished using a GABAA-receptor agonist, 4,5,6,7-tetrahydroisoxazolo(5,4-c)pyridin-3-ol (THIP) to determine if increased sleep mitigated the effects of alcohol toxicity on middle-aged flies and flies with environmentally disrupted circadian clocks mimicking groups more vulnerable to the effects of alcohol.ResultsAcute sleep deprivation increased alcohol-induced mortality following alcohol exposure. However, sleep deprivation had no effect on alcohol absorbance or clearance. Sleep deprivation also abolished functional tolerance measured 24 hours after the initial alcohol exposure, although tolerance at 4 h was observed. Pharmacologically increasing sleep prior to alcohol exposure decreased alcohol-induced mortality.ConclusionsSleep quantity prior to alcohol exposure affects alcohol toxicity with decreased sleep increasing alcohol toxicity and dampened 24-hour alcohol tolerance. In contrast, increased sleep mitigated alcohol-induced mortality even in vulnerable groups such as aging flies and those with circadian dysfunction.Statement of significanceWith the growing incidence of sleep deprivation and sleep disorders across adolescents and adults, it is important to understand the role of sleep in alcohol toxicity to develop future therapies for prevention and treatment of alcohol-induced pathologies. Using Drosophila melanogaster, an established model for both sleep and alcohol research, we found that acute and chronic sleep deprivation increased alcohol toxicity and eliminated long-term functional alcohol tolerance. In contrast, increased sleep prior to binge-like alcohol exposure mitigated alcohol-induced mortality even in vulnerable groups with higher susceptibility to alcohol toxicity.

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Pumilio Regulates Sleep Homeostasis in Response to Chronic Sleep Deprivation in Drosophila melanogaster

Frontiers in Neuroscience ◽

10.3389/fnins.2020.00319 ◽

2020 ◽

Vol 14 ◽

Author(s):

Luis A. De Jesús-Olmo ◽

Norma Rodríguez ◽

Marcelo Francia ◽

Jonathan Alemán-Rios ◽

Carlos J. Pacheco-Agosto ◽

...

Keyword(s):

Drosophila Melanogaster ◽

Sleep Deprivation ◽

Sleep Homeostasis ◽

Chronic Sleep Deprivation ◽

Chronic Sleep

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Chronic Sleep Deprivation Effects on Ischemia - Reperfusion Injury : Role of the Sympathetic Nervous System

Lebanese Medical Journal ◽

10.12816/0050217 ◽

2018 ◽

Vol 66 (3) ◽

pp. 139-143

Author(s):

Samira Choopani ◽

Mahdieh Faghihi ◽

Alireza Imani

Keyword(s):

Nervous System ◽

Sympathetic Nervous System ◽

Sleep Deprivation ◽

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Sympathetic Nervous ◽

Chronic Sleep Deprivation ◽

Chronic Sleep

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pumilio regulates sleep homeostasis in response to chronic sleep deprivation in Drosophila melanogaster

10.1101/833822 ◽

2019 ◽

Author(s):

Luis A. De Jesús-Olmo ◽

Norma Rodríguez ◽

Marcelo Francia ◽

Jonathan Alemán-Rios ◽

Carlos J. Pacheco-Agosto ◽

...

Keyword(s):

Drosophila Melanogaster ◽

Sleep Deprivation ◽

Neuronal Excitability ◽

Protein Translation ◽

Main Function ◽

Sleep Behavior ◽

Sleep Homeostasis ◽

Chronic Sleep Deprivation ◽

Underlying Mechanisms ◽

Chronic Sleep

AbstractRecent studies have identified the Drosophila brain circuits involved in the sleep/wake switch and have pointed to the modulation of neuronal excitability as one of the underlying mechanisms triggering sleep need. In this study we aimed to explore the link between the homeostatic regulation of neuronal excitability and sleep behavior in the circadian circuit. For this purpose, we selected the neuronal homeostasis protein Pumilio (Pum), whose main function is to repress protein translation and has been linked to modulation of neuronal excitability during chronic patterns of altered neuronal activity. Here we explore the effects of Pum on sleep homeostasis in Drosophila melanogaster, which shares most of the major features of mammalian sleep homeostasis. Our evidence indicates that Pum is necessary for sleep rebound and that its effect is more pronounced during chronic sleep deprivation (84 hours) than acute deprivation (12 hours). Knockdown of pum, results in a reduction of sleep rebound during acute sleep deprivation and the complete abolishment of sleep rebound during chronic sleep deprivation. These behavioral changes were associated with accompanying changes in the expression of genes involved in the regulation of neuronal excitability. Interestingly, pum knockdown also increased baseline daytime sleep, suggesting that Pum differentially regulates rebound and normal sleep. Based on these findings, we propose that Pum is a critical regulator of sleep homeostasis through neural adaptations triggered during sleep deprivation and induces rebound sleep by altering neuronal excitability.

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The neuroprotective effect of vitamin E on chronic sleep deprivation-induced memory impairment: The role of oxidative stress

Behavioural Brain Research ◽

10.1016/j.bbr.2011.09.017 ◽

2012 ◽

Vol 226 (1) ◽

pp. 205-210 ◽

Cited By ~ 105

Author(s):

Karem H. Alzoubi ◽

Omar F. Khabour ◽

Baraa Abu Rashid ◽

Imad M. Damaj ◽

Heba A. Salah

Keyword(s):

Oxidative Stress ◽

Vitamin E ◽

Sleep Deprivation ◽

Memory Impairment ◽

Neuroprotective Effect ◽

Chronic Sleep Deprivation ◽

Chronic Sleep

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Gene Networks Underlying Chronic Sleep Deprivation in Drosophila

10.21236/ada610340 ◽

2014 ◽

Author(s):

Ralph J. Greenspan

Keyword(s):

Sleep Deprivation ◽

Gene Networks ◽

Chronic Sleep Deprivation ◽

Chronic Sleep

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Daytime sleepiness and chronic sleep deprivation effects on academic performance among the Sudanese medical students

Journal of Taibah University Medical Sciences ◽

10.1016/j.jtumed.2015.05.003 ◽

2015 ◽

Vol 10 (4) ◽

pp. 467-470 ◽

Cited By ~ 5

Author(s):

Hyder O. Mirghani ◽

Mohammed A. Ahmed ◽

Abdulateef S. Elbadawi

Keyword(s):

Academic Performance ◽

Medical Students ◽

Sleep Deprivation ◽

Daytime Sleepiness ◽

Chronic Sleep Deprivation ◽

Chronic Sleep

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829 Chronic sleep deprivation in a 75-year-old female leading to micro-sleeps with atonia causing increased falls

SLEEP ◽

10.1093/sleep/zsab072.826 ◽

2021 ◽

Vol 44 (Supplement_2) ◽

pp. A323-A323

Author(s):

Neeley Remmers ◽

Michael Anderson ◽

John Nelson

Keyword(s):

Sleep Deprivation ◽

Rem Sleep ◽

Sleep Onset ◽

Exercise Intolerance ◽

Unique Case ◽

Sleep Study ◽

Obstructive Sleep ◽

History Of ◽

Chronic Sleep Deprivation ◽

Chronic Sleep

Abstract Introduction Each year, 3 million older people are treated in emergency departments for fall-related injuries. These falls can lead to serious injuries and expensive health care costs. Some have looked into the relationship between chronic sleep disturbances and falls linking chronic sleep deprivation or excessive sleep to falling. Here, we present a unique case of chronic sleep deprivation causing sleep attacks or micro-sleeps with atonia causing falls. Report of case(s) We present a 75-year-old F with a history of increased daily falls up to 4x per day that began 3 years ago. She denies any triggering events, auras, frequent tripping, loss of balance or weakness. Reportedly, she will be walking along then suddenly falls. She is aware that she is falling yet feels as though she cannot prevent/stop the fall or break her fall. No one has witnessed her fall, but is frequently found lying on the floor. She has never sustained a serious injury as a result of her falls. She has an 8 year history of restless legs syndrome treated with ropinirole and a 10 year history of obstructive sleep apnea (OSA) treated with CPAP. Her general bedtime is 2200 and wake-time is 0400 with an average 3–4 hrs of quality sleep per night for many years. She endorses severe daytime hypersomnolence and chronic hypoxemia on 3L home oxygen. We hypothesized her falls were secondary to sleep attacks or micro-sleeps where she enters REM sleep and develops atonia. Nocturnal sleep study followed by MSLT showed severe OSA with severe, persistent daytime sleeping with REM sleep and atonia. She had a mean sleep latency of 2 minutes with 1 sleep-onset REM period. We started NIPPV with supplemental oxygen treatment, and within 4 months her daytime hypersomnolence resolved, exercise intolerance improved, saturations improved to 89–90% on room air, and has <1 fall per day. Conclusion Here, we presented a unique case of a 75 yo F with recurrent falls secondary to chronic sleep deprivation causing micro-sleeps involving REM sleep and atonia. She was treated with NIPPV which improved her oxygenation and reduced her number of falls to <1 per day. Support (if any):

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Effect of Chronic Sleep Deprivation and Sleep Recovery on Hippocampal CA3 neurons, Spatial Memory and Anxiety-like behavior in Rats

Neurobiology of Learning and Memory ◽

10.1016/j.nlm.2021.107559 ◽

2021 ◽

pp. 107559

Author(s):

Konakanchi Suresh ◽

Venkateswarlu Raavi ◽

Harendra Kumar ◽

Vinutha Shankar

Keyword(s):

Sleep Deprivation ◽

Spatial Memory ◽

Hippocampal Ca3 ◽

Chronic Sleep Deprivation ◽

Ca3 Neurons ◽

Chronic Sleep

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Acute and Chronic Sleep Deprivation-Related Changes in N-methyl-D-aspartate Receptor—Nitric Oxide Signalling in the Rat Cerebral Cortex with Reference to Aging and Brain Lateralization

International Journal of Molecular Sciences ◽

10.3390/ijms20133273 ◽

2019 ◽

Vol 20 (13) ◽

pp. 3273 ◽

Cited By ~ 4

Author(s):

Zdenka Kristofikova ◽

Jana Sirova ◽

Jan Klaschka ◽

Saak V. Ovsepian

Keyword(s):

Nitric Oxide ◽

Nmda Receptor ◽

Sleep Deprivation ◽

Nmda Receptor Subunits ◽

Aspartate Receptor ◽

Age Dependent ◽

Chronic Sleep Deprivation ◽

Nos Isoforms ◽

The Impact ◽

Chronic Sleep

Aging and chronic sleep deprivation (SD) are well-recognized risk factors for Alzheimer’s disease (AD), with N-methyl-D-aspartate receptor (NMDA) and downstream nitric oxide (NO) signalling implicated in the process. Herein, we investigate the impact of the age- and acute or chronic SD-dependent changes on the expression of NMDA receptor subunits (NR1, NR2A, and NR2B) and on the activities of NO synthase (NOS) isoforms in the cortex of Wistar rats, with reference to cerebral lateralization. In young adult controls, somewhat lateralized seasonal variations in neuronal and endothelial NOS have been observed. In aged rats, overall decreases in NR1, NR2A, and NR2B expression and reduction in neuronal and endothelial NOS activities were found. The age-dependent changes in NR1 and NR2B significantly correlated with neuronal NOS in both hemispheres. Changes evoked by chronic SD (dysfunction of endothelial NOS and the increasing role of NR2A) differed from those evoked by acute SD (increase in inducible NOS in the right side). Collectively, these results demonstrate age-dependent regulation of the level of NMDA receptor subunits and downstream NOS isoforms throughout the rat brain, which could be partly mimicked by SD. As described herein, age and SD alterations in the prevalence of NMDA receptors and NOS could contribute towards cognitive decline in the elderly, as well as in the pathobiology of AD and the neurodegenerative process.

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