Newly generated neurons at 2 months post-status epilepticus are functionally integrated into neuronal circuitry in mouse hippocampus
Newly generated neurons at 2 months post-status epilepticus are functionally integrated into neuronal circuitry in mouse hippocampus
复制标题
癫痫持续状态 2 个月后新产生的神经元在功能上整合到小鼠海马的神经元回路中
DOI：
10.1016/j.expneurol.2015.09.007
复制
发表时间：
2015-11-01
影响因子：
5.3
通讯作者：
Liu, Yong
中科院分区：
文献类型：
--
作者：
Hu, Ming;Zhu, Kun;Liu, Yong
新出现的证据表明，慢性颞叶癫痫与齿状回神经发生的显著减少有关。然而，慢性癫痫海马神经发生的不同组成部分的特征仍然不清楚，特别是新生成细胞的结合。为了解决这个问题，在匹罗卡品诱导的癫痫持续状态2个月后，用增殖标志物溴脱氧尿苷（BrdU）或表达绿色荧光蛋白的逆转录病毒载体标记齿状回亚颗粒区新生细胞。通过霍乱毒素B亚基逆行示踪观察到轴突延伸到CA3区或整合到记忆回路的新生成神经元，并通过回忆空间记忆测试检测到ttle慢性期BrdU（+）细胞的激活。我们发现，在癫痫持续状态后2个月，微环境仍然能够维持新生细胞的显著神经元分化，并且颗粒细胞层中新增的神经元仍然能够在解剖学和功能上整合到神经元回路中。BrdU（+）或Ki-67（+）细胞的定量分析表明，癫痫海马中祖细胞的增殖减少，新生细胞的存活率降低。周围环境中神经营养因子水平的降低和CA3区的细胞损失可能导致慢性癫痫后新细胞的产生和存活减少。这些结果表明，慢性癫痫持续状态2个月后，慢性癫痫海马的神经发生减少与新生成神经元整合的改变无关，并且开发增加慢性癫痫海马神经发生的策略可能具有保护作用。(C) 2015爱思唯尔公司版权所有。
Emerging evidence has linked chronic temporal lobe epilepsy to dramatically reduced neurogenesis in the dentate gyrus. However, the profile of different components of neurogenesis in the chronically epileptic hippocampus is still unclear, especially the incorporation of newly generated cells. To address the issue, newly generated cells in the sub-granular zone of the dentate gyrus were labeled by the proliferation marker bromodeoxyuridine (BrdU) or retroviral vector expressing green fluorescent protein 2 months after pilocarpine-induced status epilepticus. The newly generated neurons that extended axons to CA3 area or integrated into memory circuits were visualized by cholera toxin B subunit retrograde tracing, and detecting activation of BrdU(+) cells following a recall of spatial memory test at the chronic stage of TLE. We found that the microenvironment was still able to sustain significant neuronal differentiation of newly generated cells at 2 months post-status epilepticus time-point, and newly added neurons into granular cell layer were still able to integrate into neuronal circuitry, both anatomically and functionally. Quantified analyses of BrdU(+) or Ki-67(+) cells demonstrated that there was a reduced proliferation of progenitor cells and diminished survival of newly generated cells in the epileptic hippocampus. Both decreased levels of neurotrophic factors in the surrounding milieu and cell loss in the CA3 area might contribute the decreased production of new cells and their survival following chronic epilepsy. These results suggest that decreased neurogenesis in the chronically epileptic hippocampus 2 months post status epilepticus is not associated with altered integration of newly generated neurons, and that developing strategies to augment hippocampal neurogenesis in chronic epilepsy might be protective. (C) 2015 Elsevier Inc. All rights reserved.