Histone Deacetylase Gene Expression Following Binge Alcohol Consumption in Rats and Humans
Histone Deacetylase Gene Expression Following Binge Alcohol Consumption in Rats and Humans
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DOI：
10.1111/acer.12850
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发表时间：
2015-10-01
影响因子：
3.2
通讯作者：
Gine, Elena
中科院分区：
文献类型：
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作者：
Antonio Lopez-Moreno, Jose;Marcos, Miguel;Gine, Elena
背景酗酒是过量饮酒的最常见模式之一，最近的数据表明组蛋白脱乙酰酶 (HDAC) 基因表达谱可用作精神疾病的生物标志物。方法本研究旨在表征大鼠外周血、肝脏、心脏、前额皮质和脑组织样本中 Hdac 1-11 的基因表达模式。 反复酗酒后的杏仁核，并确定大鼠和人类外周血中 Hdac 基因表达的平行性。为了实现这一目标，我们检测了大鼠、因急性酒精中毒被送往医院急诊科的患者以及经过日常操作性酒精自我管理训练的大鼠在1、4或8次饮酒（3g/kg，口服）后Hdac基因的表达。结果我们主要发现，急性饮酒降低了未曾饮酒的大鼠外周血中的基因表达（Hdac1-10） 而且这种效应在反复酗酒后会减弱。肝脏 (Hdac2,4,5) 中的 Hdac 基因表达也减少，而心脏 (Hdac1,7,8) 和杏仁核 (Hdac1,2,5) 中的表达增加。此外，在重复酗酒后 1 至 4 小时内，测量到大鼠血液中的血液酒精浓度增加，唯一发生肝性脂肪变性（脂肪肝）的组是那些暴露于 8 次酗酒事件的动物。最后，人类的暴饮暴食和大鼠的每日操作性饮酒都会增加外周血中的 HDAC 基因表达。结论我们的结果表明，外周血中 HDAC 基因表达的增加与长期饮酒有关，而在初次接触酒精后 HDAC 基因表达会减少。
BackgroundAlcohol binge drinking is one of the most common patterns of excessive alcohol use and recent data would suggest that histone deacetylases (HDACs) gene expression profiling could be useful as a biomarker for psychiatric disorders.MethodsThis study aimed to characterize the gene expression patterns of Hdac 1-11 in samples of rat peripheral blood, liver, heart, prefrontal cortex, and amygdala following repeated binge alcohol consumption and to determine the parallelism of Hdac gene expression between rats and humans in peripheral blood. To accomplish this goal, we examined Hdac gene expression following 1, 4, or 8 alcohol binges (3g/kg, orally) in the rat, in patients who were admitted to the hospital emergency department for acute alcohol intoxication, and in rats trained in daily operant alcohol self-administration.ResultsWe primarily found that acute alcohol binging reduced gene expression (Hdac1-10) in the peripheral blood of alcohol-naive rats and that this effect was attenuated following repeated alcohol binges. There was also a reduction of Hdac gene expression in the liver (Hdac2,4,5), whereas there was increased expression in the heart (Hdac1,7,8) and amygdala (Hdac1,2,5). Additionally, increased blood alcohol concentrations were measured in rat blood at 1 to 4hours following repeated alcohol binging, and the only group that developed hepatic steotosis (fatty liver) were those animals exposed to 8 alcohol binge events. Finally, both binge consumption of alcohol in humans and daily operant alcohol self-administration in rats increased Hdac gene expression in peripheral blood.ConclusionsOur results suggest that increases in HDAC gene expression within the peripheral blood are associated with chronic alcohol consumption, whereas HDAC gene expression is reduced following initial exposure to alcohol.