Contreras Ana, Morales Lidia, Tebourbi Ali, Miguéns Miguel, Olmo Nuria Del, Pérez-García Carmen
Laboratorio de Farmacología, Departamento de Ciencias Farmacéuticas y de la Salud, Facultad de Farmacia. Universidad CEU-San Pablo , 28668 Madrid, Spain.
Departamento de Psicología Básica I, Universidad Nacional de Educación a Distancia (UNED) , 28040 Madrid, Spain.
Chem Res Toxicol. 2017 Dec 18;30(12):2165-2173. doi: 10.1021/acs.chemrestox.7b00260. Epub 2017 Nov 3.
Alcohol consumption during adolescence is deleterious to the developing brain and leads to persistent deficits in adulthood. Several results provide strong evidence for ethanol-associated alterations in glutamatergic signaling and impaired synaptic plasticity in the hippocampus. Protein phosphorylation is a well-known and well-documented mechanism in memory processes, but information on phosphoprotein alterations in hippocampus after ethanol exposure is limited. This study focuses on age-related changes in the hippocampal phosphoproteome after acute alcohol administration. We have compared the phosphoprotein expression in the hippocampus of adult and adolescent Wistar rats treated with a single dose of ethanol (5 g/kg i.p.), using a proteomic approach including phosphoprotein enrichment by immobilized metal affinity chromatography (IMAC). Our proteomic analysis revealed that 13 proteins were differentially affected by age, ethanol administration, or both. Most of these proteins are involved in neuroprotection and are expressed less in young rats treated with ethanol. We conclude that acute alcohol induces important changes in the expression of phosphoproteins in the hippocampus that could increase the risk of neurodegenerative disorders, especially when the alcohol exposure begins in adolescence.
青春期饮酒对发育中的大脑有害，并会导致成年后持续存在缺陷。多项研究结果为乙醇相关的谷氨酸能信号改变以及海马体突触可塑性受损提供了有力证据。蛋白质磷酸化是记忆过程中一种广为人知且有充分文献记载的机制，但关于乙醇暴露后海马体中磷蛋白改变的信息有限。本研究聚焦于急性酒精给药后海马体磷蛋白质组中与年龄相关的变化。我们采用包括通过固定金属亲和色谱法（IMAC）富集磷蛋白的蛋白质组学方法，比较了单次给予乙醇（5 g/kg腹腔注射）处理的成年和青春期Wistar大鼠海马体中的磷蛋白表达。我们的蛋白质组学分析表明，有13种蛋白质受到年龄、乙醇给药或两者的差异影响。这些蛋白质大多参与神经保护，在接受乙醇处理的幼鼠中表达较少。我们得出结论，急性酒精会引起海马体中磷蛋白表达的重要变化，这可能会增加神经退行性疾病的风险，尤其是当酒精暴露始于青春期时。
