Hüttmann Kerstin, Sadgrove Matthew, Wallraff Anke, Hinterkeuser Stefan, Kirchhoff Frank, Steinhäuser Christian, Gray William P
Experimental Neurobiology, Neurosurgery, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn, Germany.
Eur J Neurosci. 2003 Nov;18(10):2769-78. doi: 10.1111/j.1460-9568.2003.03002.x.
Kainate-induced seizures increase hippocampal neurogenesis. Glial fibrillary acidic protein-positive astrocytes with radial processes in the dentate gyrus share many of the characteristics of radial glia and appear to act as precursor cells for adult dentate neurogenesis. Using the chemoconvulsant kainate and transgenic mice with human glial-fibrillary acidic protein (hGFAP) promoter-controlled enhanced green fluorescent protein (EGFP) expression, we examined the proliferation, morphology and electrophysiological properties of astrocytes in the neurogenic subgranular zone of the dentate gyrus in control animals and upon the induction of seizure-induced cell proliferation, three days post-kainate. EGFP-positive cells with and without radial processes could easily be distinguished. Kainate treatment caused a significant increase in the total number of proliferating EGFP-positive cells, particularly a tenfold elevation in the number of proliferating radial glia-like astrocytes, and also caused a preferential shift in the dividing cell population towards cells expressing EGFP. Immunohistochemical analysis revealed a surprisingly low proportion of cells coexpressing the astroglial marker S100beta and EGFP. Kainate increased the number of EGFP-positive, S100beta-positive and S100beta-positive-EGFP-positive astrocytes in the subgranular zone. We also report a subset of faintly EGFP-positive cells expressing markers of early neuronal differentiation. Patch-clamp analysis revealed the presence of three functionally different populations of EGFP-positive cells in both kainate and control tissue. We conclude that there is an early increase in proliferating radial glia-like astrocytes in the dentate after kainate-induced seizures, consistent with a recruitment of precursors for seizure-induced neurogenesis.
海人酸诱导的癫痫发作可增加海马神经发生。齿状回中具有放射状突起的胶质纤维酸性蛋白阳性星形胶质细胞具有许多放射状胶质细胞的特征，并且似乎充当成年齿状回神经发生的前体细胞。我们使用化学惊厥剂海人酸和具有人胶质纤维酸性蛋白（hGFAP）启动子控制的增强型绿色荧光蛋白（EGFP）表达的转基因小鼠，研究了对照动物以及海人酸注射三天后癫痫发作诱导细胞增殖时，齿状回神经源性颗粒下区星形胶质细胞的增殖、形态和电生理特性。有无放射状突起的EGFP阳性细胞很容易区分。海人酸处理导致增殖的EGFP阳性细胞总数显著增加，特别是增殖的放射状胶质细胞样星形胶质细胞数量增加了10倍，并且还导致分裂细胞群体向表达EGFP的细胞发生优先转移。免疫组织化学分析显示，共表达星形胶质细胞标志物S100β和EGFP的细胞比例出奇地低。海人酸增加了颗粒下区EGFP阳性、S100β阳性和S100β阳性-EGFP阳性星形胶质细胞的数量。我们还报告了一小部分微弱EGFP阳性细胞表达早期神经元分化标志物。膜片钳分析显示，在海人酸处理组和对照组组织中均存在三种功能不同的EGFP阳性细胞群体。我们得出结论，海人酸诱导癫痫发作后，齿状回中增殖的放射状胶质细胞样星形胶质细胞早期增加，这与癫痫发作诱导神经发生的前体细胞募集一致。
