Forensic Medicine Laboratory, Department of Oncology-Pathology Karolinska Institute, Retzius väg 3, SE-171 77, Sweden.
Forensic Medicine Laboratory, Department of Oncology-Pathology Karolinska Institute, Retzius väg 3, SE-171 77, Sweden.
Neurobiol Dis. 2018 Dec;120:63-75. doi: 10.1016/j.nbd.2018.08.011. Epub 2018 Sep 3.
Chronic alcohol abuse causes cognitive impairments associated with neurodegeneration and volume loss in the human hippocampus. Here, we hypothesize that alcohol reduces the number of granule cells in the human dentate gyrus and consequently contribute to the observed volume loss. Hippocampal samples were isolated from deceased donors with a history of chronic alcohol abuse and from controls with no alcohol overconsumption. From each case, a sample from the mid-portion of hippocampus was sectioned, immunostained for the neuronal nuclear marker NeuN, and counter stained with hematoxylin. Granule cell number and volume of granular cell layer in the dentate gyrus were estimated using stereology. We found a substantial reduction in granule cell number and also a significantly reduced volume of the granular cell layer of chronic alcohol abusers as compared to controls. In controls there was a slight age-related decline in the number of granule cells and volume of granular cell layer in line with previous studies. This was not observed among the alcoholics, possibly due to a larger impact of alcohol abuse than age on the degenerative changes in the dentate gyrus. Loss of neurons in the alcoholic group could either be explained by an increase of cell death or a reduced number of new cells added to the granular cell layer. However, there is no firm evidence for an increased neuronal death by chronic alcohol exposure, whereas a growing body of experimental data indicates that neurogenesis is impaired by alcohol. In a recent study, we reported that alcoholics show a reduced number of stem/progenitor cells and immature neurons in the dentate gyrus, hence that alcohol negatively affects hippocampal neurogenesis. The present results further suggest that such impairment of neurogenesis by chronic alcohol abuse also results in a net loss of granule cells in the dentate gyrus of hippocampus.
慢性酒精滥用会导致认知障碍，与人类海马体的神经退行性变和体积损失有关。在这里，我们假设酒精会减少人类齿状回中的颗粒细胞数量，从而导致观察到的体积损失。从有慢性酒精滥用史的已故捐赠者和没有过度饮酒的对照组中分离出海马体样本。从每个病例中，取海马体中部的样本进行切片，用神经元核标记物 NeuN 进行免疫染色，并进行苏木精复染。使用体视学法估计齿状回颗粒细胞数量和颗粒细胞层的体积。我们发现，与对照组相比，慢性酒精滥用者的颗粒细胞数量明显减少，颗粒细胞层的体积也显著减小。在对照组中，与之前的研究一致，颗粒细胞数量和颗粒细胞层的体积随着年龄的增长而略有下降。然而，在酗酒者中没有观察到这种情况，这可能是由于酒精滥用对齿状回退行性变化的影响大于年龄。酒精组神经元的丢失要么可以解释为细胞死亡增加，要么可以解释为添加到颗粒细胞层中的新细胞数量减少。然而，没有确凿的证据表明慢性酒精暴露会导致神经元死亡增加，而越来越多的实验数据表明，酒精会损害神经发生。在最近的一项研究中，我们报告说，酒精中毒者在齿状回中显示出较少的干细胞/祖细胞和未成熟神经元，因此酒精会对海马神经发生产生负面影响。目前的结果进一步表明，慢性酒精滥用对神经发生的这种损害也会导致海马齿状回颗粒细胞的净损失。
