Hans Berger Department of Neurology, Jena University Hospital, Erlanger Allee 101, 07747 Jena, Germany.
Neurosci Lett. 2013 Jun 17;545:40-5. doi: 10.1016/j.neulet.2013.04.013. Epub 2013 Apr 22.
In addition to their well known function in astrocyte coupling, gap junction forming connexins are also important for cell proliferation, migration and differentiation during brain development. The aim of this study was to determine whether loss of the main astrocytic connexins, connexin 43 (Cx43) or connexin 30 (Cx30), influences various stages of adult hippocampal neurogenesis. To that end, mice with a conditional Cx43 deletion in astrocytes and mice with a conventional knockout of Cx30 were used. We assessed cell proliferation based on Ki67-immunoreactive cell number and cell survival based on BrdU-immunoreactive cell number in the subgranular zone (SGZ) and the granular cell layer (GCL) of the dentate gyrus. The neuronal phenotype of surviving cells was analyzed following immunofluorescent co-localization of BrdU-positive cells with the neuronal markers doublecortin (DCX) and neuronal nuclear antigen (NeuN). Ablation of Cx43 in astrocytes significantly diminished proliferation and reduced the overall survival of newborn cells. In contrast, knockout of Cx30 showed a tendency towards increased proliferation and significantly enhanced the overall survival of newborn cells. The differentiation of surviving cells into neurons is unaffected following Cx43 or Cx30 knockout. Our data reveal that Cx43 promotes the survival of newborn neurons in the adult mouse hippocampus whereas Cx30 restricts their survival.
除了在星形胶质细胞偶联中具有众所周知的功能外，间隙连接形成的连接蛋白对于大脑发育过程中的细胞增殖、迁移和分化也很重要。本研究的目的是确定主要星形胶质细胞连接蛋白，连接蛋白 43（Cx43）或连接蛋白 30（Cx30）的缺失是否会影响成年海马神经发生的各个阶段。为此，使用了条件性 Cx43 缺失的星形胶质细胞小鼠和常规 Cx30 敲除的小鼠。我们根据 Ki67 免疫反应性细胞数量评估细胞增殖，根据 BrdU 免疫反应性细胞数量评估颗粒下区（SGZ）和齿状回颗粒细胞层（GCL）中的细胞存活。通过 BrdU 阳性细胞与神经元标志物双皮质素（DCX）和神经元核抗原（NeuN）的免疫荧光共定位，分析存活细胞的神经元表型。星形胶质细胞中 Cx43 的缺失显著减少了增殖并降低了新生细胞的总体存活率。相比之下，Cx30 的敲除显示出增殖增加的趋势，并显著增强了新生细胞的总体存活率。存活细胞向神经元分化不受 Cx43 或 Cx30 敲除的影响。我们的数据表明，Cx43 促进成年小鼠海马中新生神经元的存活，而 Cx30 则限制其存活。
