Study Objectives: Alcohol 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. Methods: Following 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. Results: Acute 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. Conclusions: Sleep 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.
A. Basic Sleep Science VI. Learning, Memory, Cognition90-min polysomnographically-recorded nap, with half the participants receiving CLAS. CLAS detects slow oscillations during non-rapid eye movement (NREM) sleep using a minimum negative threshold criterion coupled with online automated sleep staging, to trigger delivery of short (700 ms) auditory cues during the down-state to up-state transition (DUPT). After sleeping, participants were tested in 6 of the previously trained routes. Results: Compared with controls, the CLAS treated group was significantly faster in post-nap navigation (p<0.01). Additionally, CLAS participants showed an increase in DUPT phase-locked spindle activity in both the slow (9-12 Hz) and fast (12-16 Hz) frequency bands. Consequently, sleep deprivation represents a growing public health and economic concern due to adverse effects on individual health, cognition and productivity. Recent research in rodents suggests that sleep deprivation inhibits hippocampal dependent memory through suppression of protein synthesis; however, it remains unknown whether these interactions are conserved across learning paradigms or phylogeny. The marine mollusk Aplysia californica with a relatively simple nervous system and well-established learning paradigms has recently emerged as an excellent model system for studies of sleep deprivation and memory. Recently, we found that maintenance of steady state protein levels through concurrent inhibition of protein synthesis and protein degradation permitted the induction of long-term memory. To test the hypothesis that sleep deprivation impacts memory formation through regulation of protein levels, we investigated whether the inhibition of proteasome activity ameliorated the effects of sleep deprivation on memory. Methods: Animals were sleep deprived for 9 hours using context changes and tactile stimulation. Three hours prior to the end of sleep deprivation, animals were injected with either the proteasome inhibitor MG-132 or vehicle. Animals were trained following sleep deprivation using the learning that food is inedible paradigm, wherein animals form an association between a specific seaweed and failure of the swallowing attempts. Results: We found that pharmacological inhibition of proteasome activity during sleep deprivation permitted the induction of associative memory. Sleep deprived animals treated with MG-132 exhibited robust short-term memory whereas vehicle injected animals failed to exhibit memory. Experiments on long-term memory are ongoing. Conclusion: Inhibition of proteasome activity ameliorates memory decrements caused by sleep deprivation suggesting that sleep deprivation may inhibit the induction of memory through increased protein degradation or limitations on protein synthesis.
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