A population of neural stem cells (NSCs) dwelling in the dentate gyrus (DG) is able to generate neurons throughout adult life in the hippocampus of most mammals. These NSCs generate also astrocytes naturally and are capable of generating oligodendrocytes after gene manipulation. It has been more recently shown that adult hippocampal NSCs after epileptic seizures as well as subventricular zone NSCs after stroke can give rise to reactive astrocytes (RAs). In the hippocampus, the induction of seizures triggers the conversion of NSCs into reactive NSCs (React-NSCs) characterized by a drastic morphological transformation, abnormal migration, and massive activation or entry into the cell cycle to generate more React-NSCs that ultimately differentiate into RAs. In the search for tools to investigate the properties of React-NSCs, we have explored the LPA1–green fluorescent protein (GFP) transgenic line of mice in which hippocampal NSCs are specifically labeled due to the expression of lysophosphatidic acid receptor 1 (LPA1). We first addressed the validity of the transgene expression as true marker of LPA1 expression and then demonstrated how, after seizures, LPA1-GFP labeled exclusively React-NSCs for several weeks. Then React-NSCs lost LPA1-GFP expression as neurons of the granule cell layer started to express it. Finally, we used knockout for LPA1 transgenic mice to show that LPA1 plays a functional role in the activation of React-NSCs. Thus, we confirmed that LPA1-GFP expression is a valid tool to study both NSCs and React-NSCs and that the LPA1 pathway could be a target in the intent to preserve NSCs after seizures.

中文翻译：

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溶血磷脂酸受体 1 专门标记癫痫发作诱导的海马反应性神经干细胞并调节它们的分裂

居住在齿状回 (DG) 中的神经干细胞 (NSC) 群体能够在大多数哺乳动物的海马体中在整个成年期生成神经元。这些神经干细胞也能自然产生星形胶质细胞，并且能够在基因操作后产生少突胶质细胞。最近的研究表明，癫痫发作后的成年海马 NSC 以及中风后的脑室下区 NSC 可产生反应性星形胶质细胞 (RA)。在海马中，癫痫的诱导触发 NSCs 转化为反应性 NSCs (React-NSCs)，其特征是剧烈的形态学转变、异常迁移和大量激活或进入细胞周期以产生更多的 React-NSCs，最终分化为RA。在寻找工具来研究 React-NSCs 的特性时，我们已经探索了 LPA1-绿色荧光蛋白 (GFP) 转基因小鼠系，其中由于溶血磷脂酸受体 1 (LPA1) 的表达，海马神经干细胞被特异性标记。我们首先讨论了转基因表达作为 LPA1 表达真正标志物的有效性，然后展示了在癫痫发作后 LPA1-GFP 如何专门标记 React-NSCs 数周。然后 React-NSCs 失去 LPA1-GFP 表达，因为颗粒细胞层的神经元开始表达它。最后，我们使用敲除 LPA1 转基因小鼠来表明 LPA1 在 React-NSCs 的激活中发挥功能作用。因此，我们证实 LPA1-GFP 表达是研究 NSCs 和 React-NSCs 的有效工具，并且 LPA1 通路可能是在癫痫发作后保留 NSCs 的目标。