Alcoholism and alcohol abuse can lead to memory loss and cognitive dysfunction. The neuroinflammatory response plays an important role in the neurotoxic mechanism of chronic alcohol exposure. Additionally, the phosphorylation status of the tau protein is closely related to neurotoxicity and synaptic function. As inflammatory cytokines have been shown to regulate tau phosphorylation, in the present study, the aim was to determine whether cognitive impairment caused by chronic alcohol exposure is associated with neuroinflammation and tau hyperphosphorylation in the hippocampus. We established a chronic alcohol exposure model of C57BL/6J mice. The Y maze was used to assess the spatial recognition ability of mice, and ELISA was used to detect the levels of inflammatory cytokines IL-1β and IL-6 in the serum. Immunohistochemical and western blot assays were used to assess the expression levels of IL-1β and IL-6, as well as tau protein and its phosphorylation status in the hippocampus. We also analyzed the mRNA and protein expression of the synapse-associated proteins PSD95 and synaptophysin in the hippocampus. Our results showed that chronic alcohol exposure impaired the spatial recognition ability of mice upregulated the expression of IL-1β and IL-6 in the serum and hippocampus and increased the phosphorylation of tau protein in the hippocampus. In addition, chronic alcohol exposure downregulated PSD95 and synaptophysin protein levels. The present results indicate that hippocampal IL-1β, IL-6, and phosphorylated tau proteins may be involved in the neurotoxic mechanism of chronic alcohol exposure by mediating synaptic dysfunction.

中文翻译：

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IL-6 和 IL-1β 上调和 tau 蛋白磷酸化对小鼠海马中慢性酒精暴露的反应。

酗酒和酗酒会导致记忆力减退和认知功能障碍。神经炎症反应在慢性酒精暴露的神经毒性机制中起重要作用。此外，tau 蛋白的磷酸化状态与神经毒性和突触功能密切相关。由于炎性细胞因子已被证明可调节 tau 磷酸化，因此在本研究中，目的是确定慢性酒精暴露引起的认知障碍是否与海马中的神经炎症和 tau 过度磷酸化有关。我们建立了 C57BL/6J 小鼠的慢性酒精暴露模型。Y迷宫用于评估小鼠的空间识别能力，ELISA用于检测血清中炎性细胞因子IL-1β和IL-6的水平。免疫组织化学和蛋白质印迹分析用于评估 IL-1β 和 IL-6 的表达水平，以及 tau 蛋白及其在海马中的磷酸化状态。我们还分析了海马突触相关蛋白 PSD95 和突触素的 mRNA 和蛋白表达。我们的研究结果表明，慢性酒精暴露损害了小鼠的空间识别能力，上调了血清和海马中 IL-1β 和 IL-6 的表达，并增加了海马 tau 蛋白的磷酸化。此外，慢性酒精暴露下调 PSD95 和突触素蛋白水平。目前的结果表明，海马 IL-1β、IL-6 和磷酸化 tau 蛋白可能通过介导突触功能障碍参与慢性酒精暴露的神经毒性机制。