In the adult mouse hippocampus, new neurons are produced by radial glia-like (RGL) neural stem cells in the subgranular zone, which extend their apical processes toward the molecular layer, and express the astrocyte marker glial fibrillary acidic protein, but not the astrocyte marker S100β. In rodent models of epilepsy, adult hippocampal neurogenesis was reported to be increased after acute and mild seizures, but to be decreased by chronic and severe epilepsy. In the present study, we investigated how the severity of seizures affects neurogenesis and RGL neural stem cells in acute stages of epilepsy, using an improved mouse pilocarpine model in which pilocarpine-induced hypothermia was prevented by maintaining body temperature, resulting in a high incidence rate of epileptic seizures and low rate of mortality. In mice that experienced seizures without status epilepticus (SE), the number of proliferating progenitors and immature neurons were significantly increased, whereas no changes were observed in RGL cells. In mice that experienced seizures with SE, the number of proliferating progenitors and immature neurons were unchanged, but the number of RGL cells with an apical process was significantly reduced. Furthermore, the processes of the majority of RGL cells extended inversely toward the hilus, and about half of the aberrant RGL cells expressed S100β. These results suggest that seizures with SE lead to changes in the polarity and properties of RGL neural stem cells, which may direct them toward astrocyte differentiation, resulting in the reduction of neural stem cells producing new granule cells. This also suggests the possibility that cell polarity of RGL stem cells is important for maintaining the stemness of adult neural stem cells.

中文翻译：

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径向胶质细胞样神经干细胞的极性和特性会因癫痫持续状态的发作而改变：使用改进的小鼠毛果芸香碱癫痫模型进行研究。

在成年小鼠海马体中，新的神经元由颗粒下区的放射状胶质样 (RGL) 神经干细胞产生，将它们的顶端突起向分子层延伸，并表达星形胶质细胞标志物胶质纤维酸性蛋白，但不表达星形胶质细胞标记 S100β。在啮齿动物癫痫模型中，据报道成人海马神经发生在急性和轻度癫痫发作后增加，但在慢性和重度癫痫中减少。在本研究中，我们使用改进的小鼠毛果芸香碱模型研究癫痫发作的严重程度如何影响癫痫急性期的神经发生和 RGL 神经干细胞，其中毛果芸香碱通过维持体温来预防毛果芸香碱引起的体温过低，从而导致高发病率癫痫发作和低死亡率。在没有癫痫持续状态 (SE) 的癫痫小鼠中，增殖祖细胞和未成熟神经元的数量显着增加，而在 RGL 细胞中没有观察到变化。在经历 SE 癫痫发作的小鼠中，增殖祖细胞和未成熟神经元的数量没有变化，但具有顶端突起的 RGL 细胞数量显着减少。此外，大多数 RGL 细胞的突起向肺门反向延伸，大约一半的异常 RGL 细胞表达 S100β。这些结果表明，SE 癫痫发作导致 RGL 神经干细胞极性和特性的变化，这可能会引导它们向星形胶质细胞分化，导致产生新颗粒细胞的神经干细胞减少。