Alcoholism is a chronic relapsing disorder defined by loss of control over excessive consumption of ethanol despite damaging effects on the liver and brain. We previously showed that the overexpression in mice of Dyrk1A (TgDyrk1A, for dual-specificity tyrosine (Y) phosphorylation-regulated kinase 1A) reduces the severity of alcohol mediated liver injury. Ethanol consumption has also been associated with increased brain glutamate concentration that led to therapies targeting glutamatergic receptors and normalization of glutamatergic neurotransmission. Interestingly, mice overexpressing Dyrk1A (TgDyrk1A mice) present a reduction of glutamatergic brain transmission, which we propose could be protective against alcohol intake. To answer this question, we investigated the ethanol preference in TgDyrk1A mice using a two-bottle choice paradigm. TgDyrk1A mice showed a non-significant decrease of voluntary ethanol intake and ethanol preference compared with wild-type mice. At the peripheral level, mice overexpressing Dyrk1A show lower ethanol plasma levels, indicating a faster ethanol metabolism. At the end of the protocol, lasting 21 days, brains were extracted for protein analysis. Ethanol reduced levels of the synaptic protein PSD-95 and increased the glutamate decarboxylase GAD65, specifically in the cortex of TgDyrk1A mice. Our results suggest that overexpression of DYRK1A may cause different ethanol-induced changes in the brain.

酒精中毒是一种慢性复发性疾病，其定义为尽管对肝脏和大脑造成了破坏性影响，但仍然无法控制乙醇的过量摄入。我们以前显示，Dyrk1A（TgDyrk1A，双特异性酪氨酸（Y）磷酸化调节激酶1A）在小鼠中的过度表达降低了酒精介导的肝损伤的严重性。乙醇的消耗还与脑谷氨酸盐浓度升高有关，后者导致靶向谷氨酸能受体的疗法和谷氨酸能神经传递的正常化。有趣的是，过量表达Dyrk1A的小鼠（TgDyrk1A小鼠）降低了谷氨酸能的脑传递，我们认为这可以防止酒精摄入。为了回答这个问题，我们使用两瓶选择范例研究了TgDyrk1A小鼠的乙醇偏爱。与野生型小鼠相比，TgDyrk1A小鼠显示自愿乙醇摄入量和乙醇偏爱性没有显着降低。在外周水平，过量表达Dyrk1A的小鼠显示出较低的乙醇血浆水平，表明乙醇代谢更快。方案结束后，持续21天，提取了大脑进行蛋白质分析。乙醇降低突触蛋白PSD-95的水平，并增加谷氨酸脱羧酶GAD65，特别是在TgDyrk1A小鼠的皮质中。我们的结果表明，DYRK1A的过表达可能会导致乙醇引起的大脑变化。方案结束后，持续21天，提取了大脑进行蛋白质分析。乙醇降低突触蛋白PSD-95的水平，并增加谷氨酸脱羧酶GAD65，特别是在TgDyrk1A小鼠的皮质中。我们的结果表明，DYRK1A的过度表达可能会导致乙醇引起的大脑变化。方案结束后，持续21天，提取了大脑进行蛋白质分析。乙醇降低突触蛋白PSD-95的水平，并增加谷氨酸脱羧酶GAD65，特别是在TgDyrk1A小鼠的皮质中。我们的结果表明，DYRK1A的过表达可能会导致乙醇引起的大脑变化。