Cycles of heavy drinking and abstinence can lead to alcohol use disorder. We studied the effects of chronic intermittent ethanol exposure (CIE) over 3 weeks on neuroblastoma cells, using an ethanol concentration frequently attained in binge drinking (40 mM, 184 mg/dL). There were many changes in gene expression but most were small. CIE affected pathways instrumental in the development or plasticity of neurons, including axonal guidance, reelin signaling, and synaptogenesis. Genes involved in dopamine and serotonin signaling were also affected. Changes in transporters and receptors could dampen both NMDA and norepinephrine transmissions. Decreased expression of the GABA transporter SLC6A11 could increase GABA transmission and has been associated with a switch from sweet drinking to ethanol consumption in rats. Ethanol increased stress responses such as the unfolded protein response. TGF-β and NFκB signaling were increased. Most of the genes involved in cholesterol biosynthesis were decreased in expression. Withdrawal for 24 h after CIE caused most of the CIE-induced expression changes to move back toward unexposed levels.

中文翻译：

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慢性间歇性乙醇暴露和戒断对神经母细胞瘤细胞转录组的影响。


大量饮酒和戒酒的循环会导致酒精使用障碍。我们使用酗酒时经常达到的乙醇浓度（40 mM，184 mg/dL）研究了 3 周以上的慢性间歇性乙醇暴露 (CIE) 对神经母细胞瘤细胞的影响。基因表达有很多变化，但大多数变化很小。 CIE 影响神经元发育或可塑性的重要通路，包括轴突引导、reelin 信号传导和突触发生。参与多巴胺和血清素信号传导的基因也受到影响。转运蛋白和受体的变化可能会抑制 NMDA 和去甲肾上腺素的传输。 GABA 转运蛋白 SLC6A11 表达的减少可能会增加 GABA 的传输，并且与大鼠从甜饮料转向乙醇消耗有关。乙醇增加了应激反应，例如未折叠的蛋白质反应。 TGF-β 和 NFκB 信号传导增加。大多数参与胆固醇生物合成的基因表达减少。 CIE 后停药 24 小时导致大部分 CIE 诱导的表达变化回到未暴露水平。