Jiang Qian, Wu Ye, Wang Jingmin, Wu Xiru, Qin Jiong, Jiang Yuwu
Department of Pediatrics, Peking University First Hospital, Beijing, China.
Int J Dev Neurosci. 2010 Oct;28(6):455-63. doi: 10.1016/j.ijdevneu.2010.06.006. Epub 2010 Jun 25.
The developing brain undergoes major reorganization in response to early environmental changes. The elevated excitation that allows the neonatal brain to develop quickly also makes it highly vulnerable to age-specific seizures that can cause lifelong cognitive and neurological disability. However, it is not yet clear how seizures interfere with the developmental program and how epileptogenesis actualize. Here, by using an in vitro model, we report a global abnormal status of cortical cells after epileptiform activity was induced: more NR2B is targeted on the neuronal surface with less NR2A. Dendrotoxicity including dendritic beading, distortion and simplification of dendritic branching patterns were observed. Early-life seizure-like insults also exert effects on the excitatory synaptic size and interactions between PSD-95 and NR2A or NR2B receptor subunits. Our findings support an abnormal development or, worse, cellular degeneration that resembles immature cells, which may enlighten better understanding of the pathological mechanism of early-life seizures and its related injury.
发育中的大脑会因早期环境变化而经历重大重组。新生儿大脑快速发育所依赖的兴奋性升高,也使其极易遭受特定年龄段的癫痫发作,而这些发作可能导致终身认知和神经功能残疾。然而,癫痫发作如何干扰发育程序以及癫痫发生的具体机制尚不清楚。在此,我们通过使用体外模型报告了诱导癫痫样活动后皮质细胞的整体异常状态:更多的NR2B定位于神经元表面,而NR2A较少。观察到树突毒性,包括树突串珠、树突分支模式的扭曲和简化。早期类似癫痫发作的损伤也会对兴奋性突触大小以及PSD-95与NR2A或NR2B受体亚基之间的相互作用产生影响。我们的研究结果支持一种异常发育,或者更糟的是,类似于未成熟细胞的细胞退化,这可能有助于更好地理解早期癫痫发作的病理机制及其相关损伤。