Departamento de Ciencias Farmacéuticas y de la Salud, Facultad de Farmacia , Universidad CEU-San Pablo , Madrid 28003 , Spain.
Chem Res Toxicol. 2020 Feb 17;33(2):448-460. doi: 10.1021/acs.chemrestox.9b00359. Epub 2020 Jan 23.
Alcohol consumption during adolescence is known to cause different impairments in the hippocampus that could lead to persistent deficits in adulthood. A common pattern of alcohol use in adolescents consists of excessive and intermittent alcohol consumption over a very short period of time (binge drinking). Protein phosphorylation is a mechanism underlying memory processes and we have previously demonstrated changes in the rat hippocampal phosphoproteome after a single dose of ethanol; however, studies showing the phosphoprotein alterations in the hippocampus after repeated exposition to alcohol are limited. This study focuses on the identification of the phosphoproteins differentially regulated in the adolescent rat hippocampus after repeated ethanol administration by comparing different patterns of alcohol treatments according to dose and frequency of administration ((i) moderate dose-chronic use, (ii) low dose-intermittent use, and (iii) high dose-intermittent use). We have used a proteomic approach, including phosphoprotein enrichment by immobilized metal affinity chromatography, which revealed 21 proteins differentially affected depending on the pattern of alcohol treatment used. Many of these proteins are included in glycolysis and glucagon signaling pathways and are also involved in neurodegeneration, which could reinforce the role of metabolic alterations in the neural damage induced by repeated alcohol exposure during adolescence.
青少年饮酒已知会导致海马体的不同损伤，从而导致成年后持续出现缺陷。青少年饮酒的一种常见模式是在很短的时间内过度和间歇性地饮酒（ binge drinking ）。蛋白质磷酸化是记忆过程的一种机制，我们之前已经证明了单次给予乙醇后大鼠海马体磷酸蛋白组的变化；然而，显示重复暴露于酒精后海马体中磷酸蛋白改变的研究是有限的。这项研究侧重于通过比较根据剂量和给药频率（（i）中等剂量慢性使用，（ii）低剂量间歇性使用，和（iii）高剂量间歇性使用）的不同酒精处理方式，鉴定在重复给予乙醇后青少年大鼠海马体中差异调节的磷酸蛋白。我们使用了一种蛋白质组学方法，包括通过固定金属亲和层析进行磷酸蛋白富集，这揭示了 21 种根据所用酒精处理方式而差异受影响的蛋白。这些蛋白中的许多蛋白都包含在糖酵解和胰高血糖素信号通路中，并且还参与神经退行性变，这可能会加强代谢改变在青少年时期反复暴露于酒精引起的神经损伤中的作用。
