Department of Pharmaceutical Sciences, The University of Kentucky College of Pharmacy, 789 S. Limestone, BPC 022A, Lexington, KY 40536-0596, USA.
Neuroscience. 2011 Dec 1;197:381-93. doi: 10.1016/j.neuroscience.2011.09.019. Epub 2011 Sep 16.
Excessive alcohol intake, characteristic of an alcohol use disorder (AUD), results in neurodegeneration as well as cognitive deficits that may recover in abstinence. Neurodegeneration in psychiatric disorders such as AUDs is due to various effects on tissue integrity. Several groups report that alcohol-induced neurodegeneration and recovery include a role for adult neurogenesis. Therefore, the initial purpose of this study was to investigate the effect of alcohol on the temporal profile of neural progenitor cells using the radial glia marker, vimentin, in a model of an AUD. However, striking vimentin expression throughout corticolimbic regions led, instead, to the discovery of a significant gliosis response in this model. Adult male rats were subjected to a 4-day binge model of an AUD and brains harvested for immunohistochemistry at 0, 2, 4, 7, 14, and 28 days following the last dose of ethanol. A prominent increase in vimentin immunoreactivity was apparent at 4 and 7 days post binge that returned to control levels by 14 days in the corticolimbic regions examined. Vimentin-positive cells co-labeled with glial fibrillary acidic protein (GFAP), which suggested that cells were reactive astrocytes. A second experiment supported that increased vimentin was not primarily due to alcohol withdrawal seizures and is more likely due to alcohol-induced cell death. As this gliosis was remarkably distinct in regions where cell death had not previously been reported in this model, adjacent tissue sections were processed for FluoroJade B staining for cell death. FluoroJade B-positive cells were evident immediately following the last ethanol dose as expected, but were significantly elevated in the hippocampal dentate gyrus and CA3 regions and corticolimbic regions from 2 to 7 days post binge. Intriguingly, vimentin labeling of astrogliosis is more widespread than FluoroJade B labeling of cell death, which suggests that 4-day binge ethanol consumption is more damaging than originally realized.
过量饮酒是酒精使用障碍（AUD）的特征，可导致神经退行性变和认知缺陷，这些缺陷在戒酒后可能会恢复。 AUD 等精神疾病中的神经退行性变是由于对组织完整性的各种影响造成的。有几个研究小组报告称，酒精引起的神经退行性变和恢复与成体神经发生有关。因此，本研究的最初目的是使用径向胶质标志物 vimentin 研究 AUD 模型中酒精对神经祖细胞时间分布的影响。然而，在皮质边缘区域发现的 vimentin 表达的惊人增加，导致在该模型中发现了明显的神经胶质反应。雄性成年大鼠接受为期 4 天的 AUD binge 模型，在最后一次乙醇剂量后 0、2、4、7、14 和 28 天收获大脑，用于免疫组织化学分析。在 binge 后 4 和 7 天，vimentin 免疫反应明显增加，在检查的皮质边缘区域中，14 天恢复到对照水平。 vimentin 阳性细胞与胶质纤维酸性蛋白（GFAP）共标记，这表明细胞是反应性星形胶质细胞。第二项实验支持增加的 vimentin 不是主要由于酒精戒断性癫痫发作，更可能是由于酒精引起的细胞死亡。由于这种神经胶质反应在该模型中先前没有报道过细胞死亡的区域中非常明显，因此对相邻组织切片进行 FluoroJade B 染色以检测细胞死亡。正如预期的那样，FluoroJade B 阳性细胞在最后一次乙醇剂量后立即出现，但在 binge 后 2 至 7 天的海马齿状回和 CA3 区域以及皮质边缘区域中显著升高。有趣的是，星形胶质细胞增生的 vimentin 标记比 FluoroJade B 标记的细胞死亡更为广泛，这表明 4 天 binge 乙醇消耗比最初认识到的更为有害。
