The polarity and properties of radial glia-like neural stem cells are altered by seizures with status epilepticus: Study using an improved mouse pilocarpine model of epilepsy
The polarity and properties of radial glia-like neural stem cells are altered by seizures with status epilepticus: Study using an improved mouse pilocarpine model of epilepsy
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DOI：
10.1002/hipo.23153
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发表时间：
2019-09-05
期刊：
影响因子：
3.5
通讯作者：
Seki, Tatsunori
中科院分区：
文献类型：
--
作者：
Sasaki-Takahashi, Natsu;Shinohara, Hiroshi;Seki, Tatsunori
在成年小鼠海马中，新的神经元是由颗粒下区的放射状胶质样（RGL）神经干细胞产生的，这些神经干细胞将其顶端突起向分子层延伸，并表达星形胶质细胞标志物胶质细胞酸性蛋白，但不表达星形胶质细胞标志物S100 β。在啮齿类动物癫痫模型中，成人海马神经发生据报道在急性和轻度癫痫发作后增加，但在慢性和重度癫痫发作后减少。在本研究中，我们研究了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，使用改进的小鼠毛果芸香碱模型，其中毛果芸香碱诱导的低温通过保持体温来预防，从而导致癫痫发作的高发病率和低死亡率。在没有癫痫持续状态（SE）的癫痫发作小鼠中，增殖祖细胞和未成熟神经元的数量显著增加，而RGL细胞没有观察到变化。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细胞的数量显著减少。此外，大多数RGL细胞的突起向门部反向延伸，约一半的异常RGL细胞表达S100 β。这些结果表明，癫痫发作与SE导致RGL神经干细胞的极性和性质的变化，这可能会引导他们向星形胶质细胞分化，从而减少神经干细胞产生新的颗粒细胞。这也表明RGL干细胞的细胞极性对于维持成体神经干细胞的干细胞性是重要的。
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 S100 beta. 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 S100 beta. 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.