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单次 binge 饮酒会导致睡眠障碍,破坏睡眠稳态,并下调平衡核苷转运蛋白 1。

A single episode of binge alcohol drinking causes sleep disturbance, disrupts sleep homeostasis, and down-regulates equilibrative nucleoside transporter 1.

机构信息

Harry S. Truman Memorial Veterans Hospital and Department of Neurology, School of Medicine, University of Missouri- Columbia, Columbias, Missouri, USA.

出版信息

J Neurochem. 2018 Aug;146(3):304-321. doi: 10.1111/jnc.14470.

Abstract

Binge alcohol drinking, a risky pattern of alcohol consumption, has severe consequences toward health and well-being of an individual, his family, and society. Although, binge drinking has detrimental effects on sleep, underlying mechanisms are unknown. We used adult male C57BL/6J mice and exposed them to a single, 4-h session of binge alcohol self-administration, in stress-free environment, to examine neuronal mechanisms affecting sleep. We first verified binge pattern of alcohol consumption. When allowed to self-administer alcohol in a non-stressful environment, mice consumed alcohol in a binge pattern. Next, effect of binge drinking on sleep-wakefulness was monitored. While sleep-wakefulness remained unchanged during drinking session, significant increase in non-rapid eye movement (NREM) sleep was observed during 4 h of active period post-binge, followed by increased wakefulness, reduced sleep during subsequent sleep (light) period; although the timing of sleep onset (at lights-on) remained unaffected. Next, electrophysiological and biochemical indicators of sleep homeostasis were examined using sleep deprivation-recovery sleep paradigm. Mice exposed to binge drinking did not show an increase in cortical theta power and basal forebrain adenosine levels during sleep deprivation; NREM sleep and NREM delta power did not increase during recovery sleep suggesting that mice exposed to binge alcohol do not develop sleep pressure. Our final experiment examined expression of genes regulating sleep homeostasis following binge drinking. While binge drinking did not affect adenosine kinase and A1 receptor, expression of equilibrative nucleoside transporter 1 (ENT1) was significantly reduced. These results suggest that binge alcohol consumption-induced down-regulation of ENT1 expression may disrupt sleep homeostasis and cause sleep disturbances. Open Data: Materials are available on https://cos.io/our-services/open-science-badges/ https://osf.io/93n6m/.

摘要

binge 饮酒,即一种危险的饮酒模式,会对个人、家庭和社会的健康和幸福造成严重后果。尽管 binge 饮酒对睡眠有不良影响,但具体的机制尚不清楚。我们使用成年雄性 C57BL/6J 小鼠,在无压力的环境下让它们进行单次 4 小时的 binge 酒精自我给药,以研究影响睡眠的神经元机制。我们首先验证了 binge 饮酒模式。当允许它们在无压力的环境下自行摄取酒精时,小鼠会 binge 式地摄取酒精。接下来,监测 binge 饮酒对睡眠-觉醒的影响。虽然在饮酒期间睡眠-觉醒没有变化,但在 binge 后 4 小时的活跃期观察到非快速眼动 (NREM) 睡眠显著增加,随后觉醒增加,随后的睡眠(浅睡)期间睡眠减少;尽管睡眠开始的时间(在光照开始时)不受影响。接下来,使用睡眠剥夺-恢复睡眠范式检查睡眠稳态的电生理和生化指标。暴露于 binge 饮酒的小鼠在睡眠剥夺期间没有显示皮质θ波功率和基底前脑腺苷水平增加;在恢复睡眠期间,NREM 睡眠和 NREM 德尔塔波功率没有增加,这表明暴露于 binge 酒精的小鼠不会产生睡眠压力。我们的最后一个实验研究了 binge 饮酒后调节睡眠稳态的基因表达。虽然 binge 饮酒不会影响腺苷激酶和 A1 受体,但平衡核苷转运蛋白 1 (ENT1) 的表达显著降低。这些结果表明,binge 饮酒引起的 ENT1 表达下调可能破坏睡眠稳态并导致睡眠障碍。开放数据:材料可在 https://cos.io/our-services/open-science-badges/ https://osf.io/93n6m/ 上获得。

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