Mohammed Hassan E, Nelson James C, Marshall S Alex
Department of Biological & Biomedical Sciences, North Carolina Central University, Durham, NC 27707, USA.
Neuroglia. 2024 Sep;5(3):289-305. doi: 10.3390/neuroglia5030020. Epub 2024 Aug 2.
Alzheimer's disease (AD) is the most common form of dementia with characteristic biological markers. Clinically, AD presents as declines in memory, reasoning, and decision making, but the loss of memory is particularly associated with hippocampal damage. Likewise, excessive ethanol consumption has been found to disrupt hippocampal function and integrity. To assess the potential shared consequences of AD pathology and ethanol, 5xFAD mice were administered 5 g/kg ethanol daily for 10 days. Immunohistochemical analysis revealed ethanol and AD converged to lead to microglial and astrocytic senescence as well as increased Aß-plaque formation in the hippocampus. Despite the exacerbation of these potential mechanisms of neurodegeneration, there were no additive effects of ethanol exposure and AD-related genotype on Fluoro-Jade C (FJC)+ cells or cognitive deficits in the novel object recognition task. Overall, these results are the first to characterize the effects of ethanol exposure on early adulthood in the 5xFAD mouse model. Together these findings support the idea that alcohol can influence AD pathology; however, the mechanisms involved in AD progression (e.g., glial activation and Aß-plaque) may be impacted prior to evidence of pathology (e.g., cognitive decline or neuronal loss).
阿尔茨海默病（AD）是最常见的具有特征性生物标志物的痴呆形式。临床上，AD表现为记忆、推理和决策能力下降，但记忆丧失尤其与海马体损伤有关。同样，已发现过量饮酒会破坏海马体功能和完整性。为了评估AD病理和乙醇的潜在共同后果，对5xFAD小鼠每天给予5 g/kg乙醇，持续10天。免疫组织化学分析显示，乙醇和AD共同导致小胶质细胞和星形胶质细胞衰老以及海马体中Aβ斑块形成增加。尽管这些神经退行性变的潜在机制加剧，但在新物体识别任务中，乙醇暴露和AD相关基因型对氟玉红C（FJC）+细胞或认知缺陷没有累加效应。总体而言，这些结果首次描述了乙醇暴露对5xFAD小鼠模型成年早期的影响。这些发现共同支持了酒精会影响AD病理的观点；然而，AD进展所涉及的机制（如神经胶质激活和Aβ斑块）可能在病理证据（如认知衰退或神经元丧失）出现之前就受到影响。
