Ablation of aberrant neurogenesis fails to attenuate cognitive deficit of chronically epileptic mice
Ablation of aberrant neurogenesis fails to attenuate cognitive deficit of chronically epileptic mice
复制标题
消除异常神经发生未能减轻慢性癫痫小鼠的认知缺陷
DOI：
10.1016/j.eplepsyres.2018.03.004
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发表时间：
2018-05
影响因子：
2.2
通讯作者：
Jian-Xin Liu
中科院分区：
文献类型：
--
作者：
Kun Zhu;Bo Yuan;Ming Hu;Cheng-Jun Li;Jie-Hua Xu;Gai-Feng Feng;Yong Liu;Jian-Xin Liu
匹鲁卡品诱导的急性癫痫发作强烈诱导异常海马神经发生，其特征在于神经祖细胞增殖增加和新生成的颗粒细胞异常整合-门异位颗粒细胞（EGC），苔藓纤维发芽（MFS）和门基底树突（HBD），这可能会干扰海马神经元回路，从而导致颞叶癫痫（TLE）患者和动物模型的认知障碍。先前的研究通过消融急性癫痫发作后海马神经发生产生不一致的结果，关于长期认知障碍的发展。此外，在这些研究中，慢性癫痫海马中随后的异常整合的充分减少并没有得到很好的建立。因此，癫痫引起的海马神经发生异常与癫痫相关的认知功能下降之间的联系仍有待澄清。在这项研究中，在匹鲁卡品诱导的癫痫持续状态（SE）之前和之后，给小鼠注射甲基偶氮甲醇乙酸酯（MAM），以实现有助于病理募集的新生细胞的整体消融。此外，考虑到新生颗粒细胞需要相当长的时间才能充分发育异常整合，特别是MFS，因此选择了一个较长的时间点进行行为测试。尽管在消融方案后确认了异常整合（包括EGC、MFS和HBD）的总体减少，但消融和非消融小鼠在Morris水迷宫（MWM）任务中的表现没有差异。因此，目前的研究结果提供了新的证据，即至少在本研究中使用的模型中，神经发生的消融与异常整合的总体减少不能减轻随后的认知障碍。
Pilocarpine-induced acute seizures strongly induce aberrant hippocampal neurogenesis, characterized by increased proliferation of neural progenitors and abnormal integrations of newly generated granule cells − hilar ectopic granule cells (EGCs), mossy fibre sprouting (MFS), and hilar basal dendrites (HBDs), which may disturb hippocampal neuronal circuits and thus contribute to cognitive impairment in temporal lobe epilepsy (TLE) patients and animal models. Previous studies via ablating hippocampal neurogenesis after acute seizures produced inconsistent results regarding the development of long-term cognitive impairment. Furthermore, a sufficient decrease of subsequent abnormal integrations in chronically epileptic hippocampus was not well-established in these studies. Therefore, the link between seizure-induced aberrant hippocampal neurogenesis and cognitive decline associated with epilepsy is still in need to be clarified. In this study, the mice were injected with methylazoxymethanol acetate (MAM) both before and after pilocarpine-induced status epilepticus (SE) to achieve an overall ablation of newborn cells contributing to the pathological recruitment. In addition, a protracted.time point was chosen for behavioral testing considering it takes a fairly long time for newborn granule cells to adequately develop abnormal integrations, especially MFS. Although an overall reduction of abnormal integrations, including EGCs, MFS and HBDs was confirmed following the ablation regime, the performance of ablated and non-ablated mice in the Morris Water Maze (MWM) task did not differ. The current findings.therefore provide novel evidences that ablation of neurogenesis with an overall decrease of abnormal integrations cannot attenuate subsequent cognitive impairment at least in the model used in this study.
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影响因子：
6.1
作者：
A. Pekcec;M. Mühlenhoff;R. Gerardy-Schahn;H. Potschka
通讯作者：
A. Pekcec;M. Mühlenhoff;R. Gerardy-Schahn;H. Potschka
影响因子：
5.6
作者：
MELLO, LEAM;CAVALHEIRO, EA;FINCH, DM
通讯作者：
FINCH, DM
影响因子：
5.3
作者：
Kron, Michelle M.;Zhang, Helen;Parent, Jack M.
通讯作者：
Parent, Jack M.
影响因子：
2.2
作者：
K. Zhu;Bo Yuan;Ming Hu;Gai-feng Feng;Yong Liu;Jianxin Liu
通讯作者：
K. Zhu;Bo Yuan;Ming Hu;Gai-feng Feng;Yong Liu;Jianxin Liu
DOI：
10.1016/0013-4694(72)90177-0
发表时间：
1972-01-01
期刊：
ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY
影响因子：
--
作者：
RACINE, RJ
通讯作者：
RACINE, RJ