Forced Physical Training Increases Neuronal Proliferation and Maturation with Their Integration into Normal Circuits in Pilocarpine Induced Status Epilepticus Mice
Forced Physical Training Increases Neuronal Proliferation and Maturation with Their Integration into Normal Circuits in Pilocarpine Induced Status Epilepticus Mice
复制标题
强迫体能训练可促进毛果芸香碱诱发癫痫持续状态小鼠的神经元增殖和成熟，并融入正常回路。
DOI：
10.1007/s11064-019-02877-3
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发表时间：
2019-11-01
影响因子：
4.4
通讯作者：
Liu, Yong
中科院分区：
文献类型：
--
作者：
Iqbal, Muneeb;Xiao, Xin-Li;Liu, Yong
在癫痫持续状态（SE）后的潜伏期产生的新生神经元数量增加有助于海马的异常重新布线，并被假设促进癫痫发生。尽管有报道称体育训练（PT）会导致SE后神经发生进一步增加，但PT如何影响它们的整合模式仍是未知的，它们是整合到正常回路中还是增加了异常整合。为了了解PT影响SE的基本机制，并阐明神经元整合在SE预后中的可能作用，我们评估了成年雄性小鼠在匹罗卡品诱导SE后进行4周的跑步机PT对行为和异常整合参数的影响。在潜伏期（2周），还测量了海马中BDNF基因甲基化及其蛋白水平的变化，以探索参与增加神经发生的潜在途径。我们的研究结果表明，尽管PT增加了齿状回神经元的增殖和成熟，但与未运动的SE小鼠相比，通过减少异位颗粒细胞、门叶基底树突和苔藓纤维发芽的数量，它们显示出与海马回路的异常整合减少。虽然SE降低了BDNF基因启动子特定CpGs的甲基化百分比，但与未运动的SE小鼠相比，PT在BDNF CpGs甲基化方面没有产生任何显著差异。综上所述，PT通过除去甲基化BDNF CpGs外的一些途径增加BDNF水平，从而促进海马神经发生，并使SE后新生神经元融入正常回路，从而减少自发性复发性癫痫发作，增强空间记忆。图形
Increased number of newly-born neurons produced at latent stage after status epilepticus (SE) contribute to aberrant rewiring of hippocampus and are hypothesized to promote epileptogenesis. Although physical training (PT) was reported to cause further increase in neurogenesis after SE, how PT affect their integration pattern is still elusive, whether they integrate into normal circuits or increase aberrant integrations is yet to be determined. To understand this basic mechanism by which PT effects SE and to elaborate the possible role of neuronal integrations in prognosis of SE, we evaluated the effect of 4 weeks of treadmill PT in adult male mice after pilocarpine-induced SE on behavioral and aberrant integrations' parameters. Changes in BDNF gene methylation and its protein level in hippocampus was also measured at latent stage (2-weeks) to explore underlying pathways involved in increasing neurogenesis. Our results demonstrated that although PT increased proliferation and maturation of neurons in dentate gyrus, they showed reduced aberrant integrations into hippocampal circuitry assessed through a decrease in the number of ectopic granular cells, hilar basal dendrites and mossy fiber sprouting as compared to non-exercised SE mice. While SE decreased the percentage methylation of specific CpGs of BDNF gene's promoter, PT did not yield any significant difference in methylation of BDNF CpGs as compared to non-exercised SE mice. In conclusion, PT increases hippocampal neurogenesis through increasing BDNF levels by some pathways other than demethylating BDNF CpGs and causes post SE newly-born neurons to integrate into normal circuits thus resulting in decreased spontaneous recurrent seizures and enhanced spatial memory. Graphic