Department of Biological & Biomedical Sciences, North Carolina Central University, Durham, NC, 27707, United States.
Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, 27708, United States.
Alcohol. 2022 May;100:31-39. doi: 10.1016/j.alcohol.2022.02.002. Epub 2022 Feb 17.
Adolescent alcohol abuse is a significant public health concern, with approximately 4.3 million U.S. adolescents reporting monthly binge drinking. Excessive ethanol consumption during adolescence has been linked to dysregulation of the neuroimmune system, particularly in the hippocampus. Because there are sex differences in both neuroimmune responses and ethanol's pharmacologic actions, this study tested whether there were disparate effects based on sex in glial cells and neurodegeneration in adulthood after the adolescent intermittent ethanol (AIE) model. Male and female adolescent Sprague-Dawley rats underwent AIE. In adulthood, immunohistochemical techniques were utilized to determine the effects of AIE on astrocytes and microglia, and Fluoro-Jade C (FJC) was used to assess neurodegeneration in the hippocampus. AIE exposure significantly increased astrocyte activation in the cornu ammonis 1 (CA1), CA2/3, and dentate gyrus (DG) in both male and female rats with no discernible sex differences in immunoreactivity. Likewise, the number of GFAP + cells was significantly increased by AIE across the hippocampus. In our microglial assessment, AIE only led to increased Iba1 immunoreactivity in the CA1 but not CA2/3 or DG regions. However, the number of Iba1+ cells was increased by AIE in both the CA1 and DG subregions. In the DG, the ethanol effect was observed in both sexes, but in the CA1, AIE-induced increased Iba1 cells were only observed in females. In regard to neurodegeneration, there were no persisting AIE effects on FJC + cells. These findings indicate that AIE alters hippocampal glial cells in adulthood, in the absence of active neurodegeneration. However, while AIE induced long-term elevation of astroglial measures in both males and females, persisting AIE-induced microglial activation was more sparse and sex-dependent. While the majority of these findings suggest that AIE has similar effects on glial morphology and number between males and females, additional work should determine whether there are molecular differences as well as innate sex differences in glial interaction with AIE's influence on glial functions in behavior.
青少年酗酒是一个严重的公共卫生问题，约有 430 万美国青少年报告每月 binge drinking。青少年时期过量饮酒会导致神经免疫调节失调，特别是在海马体中。由于神经免疫反应和乙醇药理作用在性别上存在差异，因此本研究测试了在青少年间歇性乙醇（AIE）模型后，基于性别的胶质细胞和成年期神经退行性变是否存在不同的影响。雄性和雌性青少年 Sprague-Dawley 大鼠接受 AIE 处理。成年后，采用免疫组织化学技术确定 AIE 对星形胶质细胞和小胶质细胞的影响，并用 Fluoro-Jade C（FJC）评估海马体中的神经退行性变。AIE 暴露显著增加了雄性和雌性大鼠 CA1、CA2/3 和齿状回（DG）中的星形胶质细胞激活，且免疫反应无明显性别差异。同样，AIE 使整个海马体中的 GFAP+细胞数量显著增加。在我们的小胶质细胞评估中，AIE 仅导致 CA1 中 Iba1 免疫反应增加，而 CA2/3 或 DG 区域则没有。然而，AIE 使 CA1 和 DG 亚区中的 Iba1+细胞数量增加。在 DG 中，乙醇的作用在两性中均可见，但在 CA1 中，仅在雌性中观察到 AIE 诱导的 Iba1 细胞增加。关于神经退行性变，FJC+细胞没有持续的 AIE 影响。这些发现表明，AIE 在没有主动神经退行性变的情况下，改变成年期海马体中的神经胶质细胞。然而，虽然 AIE 在雄性和雌性中均诱导长期的星形胶质细胞测量值升高，但持续的 AIE 诱导的小胶质细胞激活更为稀疏且具有性别依赖性。虽然这些发现中的大多数表明 AIE 对雄性和雌性的神经胶质形态和数量具有相似的影响，但还需要进一步的工作来确定是否存在分子差异以及神经胶质与 AIE 对神经胶质功能影响之间的内在性别差异与行为有关。
