Alcohol consumption induces global gene expression changes in VTA dopaminergic neurons.
Alcohol consumption induces global gene expression changes in VTA dopaminergic neurons.
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DOI：
10.1111/gbb.12266
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发表时间：
2016-03
期刊：
影响因子：
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通讯作者：
Ponomarev I
中科院分区：
文献类型：
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作者：
Marballi K;Genabai NK;Blednov YA;Harris RA;Ponomarev I
酗酒与调节动机和目标导向行为的神经回路失调有关。腹侧被盖区（VTA）和伏隔核之间的多巴胺能连接被视为介导酒精奖赏和行为影响的神经回路的关键组成部分。我们试图确定酗酒对 VTA 多巴胺能 (DA) 神经元整体基因表达的影响。偏好酒精的 C57BL/6J × FVB/NJ F1 杂交雌性小鼠接受改良的黑暗饮酒 (DID) 程序 3 周，而对照动物只能喝水。使用微阵列测量激光捕获的酪氨酸羟化酶阳性 VTA DA 神经元的整体基因表达。饮酒和不饮酒小鼠之间有 644 个转录本存在差异表达，而酒精组中有 930 个转录本与最后两天饮酒期间的酒精摄入量相关。对酒精反应基因的生物信息学分析确定了因饮酒而扰乱 DA 神经元的分子途径和网络，其中包括神经免疫和表观遗传功能、酒精代谢和大脑疾病。大多数在 DA 神经元中高表达和特异表达的基因都受到饮酒量的下调或呈负相关，这表明高饮酒动物中 DA 神经元的活性降低。多巴胺能转录组的这些变化为酒精诱导的神经适应奠定了基础，这可能在成瘾的过渡中发挥着至关重要的作用。
Alcoholism is associated with dysregulation in the neural circuitry that mediates motivated and goal-directed behaviors. The dopaminergic connection between the ventral tegmental area (VTA) and the nucleus accumbens is viewed as a critical component of the neurocircuitry mediating alcohol’s rewarding and behavioral effects. We sought to determine the effects of binge alcohol drinking on global gene expression in VTA dopaminergic (DA) neurons. Alcohol-preferring C57BL/6J × FVB/NJ F1 hybrid female mice were exposed to a modified drinking in the dark (DID) procedure for 3 weeks, while control animals had access to water only. Global gene expression of laser-captured tyrosine hydroxylase - positive VTA DA neurons was measured using microarrays. 644 transcripts were differentially expressed between the drinking and non-drinking mice and 930 transcripts correlated with alcohol intake during the last two days of drinking in the alcohol group. Bioinformatics analysis of alcohol-responsive genes identified molecular pathways and networks perturbed in DA neurons by alcohol consumption, which included neuroimmune and epigenetic functions, alcohol metabolism and brain disorders. The majority of genes with high and specific expression in DA neurons were down regulated by or negatively correlated with alcohol consumption, suggesting a decreased activity of DA neurons in high drinking animals. These changes in the dopaminergic transcriptome provide a foundation for alcohol-induced neuroadaptations that may play a crucial role in the transition to addiction.