当前位置: X-MOL 学术Neurosci. Lett. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Orexin gene expression is downregulated in alcohol dependent rats during acute alcohol withdrawal
Neuroscience Letters ( IF 2.5 ) Pub Date : 2020-10-01 , DOI: 10.1016/j.neulet.2020.135347
Rishi Sharma , Abhilasha Sharma , Pradeep Sahota , Mahesh M. Thakkar

Alcohol use disorders (AUD) are chronic relapsing brain disorder characterized by compulsive and heavy alcohol consumption. During acute withdrawal, patients with AUD display excessive daytime sleepiness, a condition linked to serious life-threatening complications, however, the mechanism is not known. Orexin and melanin-concentrating hormone (MCH) are the two hypothalamic neuropeptides that regulate many behaviors including sleep-wakefulness, and alcohol consumption, reinforcement, and reinstatement. Importantly, loss of orexin neurons causes narcolepsy, a severe sleep disorder with excessive daytime sleepiness. Does acute alcohol withdrawal reduce orexin gene expression? To investigate this, male Sprague-Dawley rats were divided in two groups: Rats were either administered with alcohol, mixed with infant formula (alcohol group) or control mixture containing water and infant formula (Controls) by gastric intubation every 8 h for 4 days using Majchrowicz’s chronic binge drinking protocol. The doses of alcohol were adjusted depending on degree of intoxication, exhibited by animals, prior to each dose. The animals were euthanized after 12 h of last alcohol/water administration. During withdrawal, the hypothalamus was rapidly dissected out, and the expressions of orexin and MCH genes were examined by Real-time PCR. There was a significant reduction in orexin gene expression in rats subjected to alcohol withdrawal as compared to controls. No such change was observed in the MCH gene expression. These results suggest that downregulation of orexin gene expression may be a possible mechanism responsible for excessive daytime sleepiness associated with alcohol withdrawal in patients with AUD.



中文翻译:

酒精戒断大鼠急性酒精戒断过程中Orexin基因表达下调

酒精使用障碍(AUD)是一种慢性复发性脑部疾病,其特征在于强迫和大量饮酒。在急性停药期间,AUD患者表现出过度的日间嗜睡,这种情况与严重的威胁生命的并发症有关,但该机制尚不清楚。食欲素和黑色素浓缩激素(MCH)是下丘脑的两个神经肽,可调节许多行为,包括睡眠-清醒以及饮酒,强化和恢复精神。重要的是,食欲素神经元的缺失会导致发作性睡病,这是一种严重的睡眠障碍,白天过度嗜睡。急性戒酒会降低食欲素基因表达吗?为了对此进行研究,将雄性Sprague-Dawley大鼠分为两组:给大鼠服用酒精,使用Majchrowicz的慢性暴饮方案,每8小时通过胃插管与婴儿配方食品(酒精组)或含有水和婴儿配方食品的对照混合物(对照组)混合4天。在每次给药之前,根据动物所表现出的中毒程度来调整酒精的剂量。最后一次酒精/水施用12小时后,对动物实施安乐死。停药期间,迅速切出下丘脑,并通过实时荧光定量PCR检测orexin和MCH基因的表达。与对照组相比,酒精戒断大鼠的食欲素基因表达显着降低。在MCH基因表达中未观察到这种变化。

更新日期:2020-10-05
down
wechat
bug