Jiang Wen, Wan Qi, Zhang Zhi-Jun, Wang Wei-Dong, Huang Yuan-Gui, Rao Zhi-Ren, Zhang Xia
Department of Neurology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
Brain Res. 2003 Jul 11;977(2):141-8. doi: 10.1016/s0006-8993(03)02438-7.
Epileptic seizures originating from the limbic system have been shown to stimulate the proliferation rate of granule cell precursors in the adult brain, but it is not clear if other type(s) of seizures have the similar effects. This study examined the effects of pentylenetrazol (PTZ)-induced generalized clonic seizures on dentate granule cell neurogenesis in adult rats. Using systemic bromodeoxyuridine (BrdU) to label dividing cells, we studied the proliferation rate of neural precursor cells in the dentate gyrus at various time points after PTZ-induced seizures. The double-label immunofluorescence with confocal microscopy was used to determine the newborn cell phenotypes. Quantitative analysis of BrdU labeling revealed a significant increase in the proliferation rate of neural precursor cells in the dentate gyrus 3, 7, and 14 days after seizures. The number of BrdU-labeled cells in the dentate gyrus returned to baseline levels by 28 days after the initial seizures. Most of newborn cells migrated into the granule cell layer from the subgranular zone, displayed the neuronal phenotype, and developed morphological characteristics of differentiated dentate granule cells. These results indicated that neuron proliferation in the dentate gyrus was enhanced during a time window (3-14 days) after PTZ-induced seizures. Its underlying mechanism is discussed.
源自边缘系统的癫痫发作已被证明会刺激成年大脑中颗粒细胞前体的增殖速率，但尚不清楚其他类型的癫痫发作是否具有类似作用。本研究检测了戊四氮（PTZ）诱导的全身性阵挛性癫痫发作对成年大鼠齿状颗粒细胞神经发生的影响。使用全身注射溴脱氧尿苷（BrdU）标记分裂细胞，我们研究了PTZ诱导癫痫发作后不同时间点齿状回中神经前体细胞的增殖速率。采用共聚焦显微镜双标免疫荧光法确定新生细胞表型。对BrdU标记的定量分析显示，癫痫发作后3天、7天和14天，齿状回中神经前体细胞的增殖速率显著增加。首次癫痫发作后28天，齿状回中BrdU标记细胞的数量恢复到基线水平。大多数新生细胞从颗粒下区迁移到颗粒细胞层，表现出神经元表型，并发育出分化的齿状颗粒细胞的形态特征。这些结果表明，PTZ诱导癫痫发作后的一个时间窗（3 - 14天）内，齿状回中的神经元增殖增强。文中讨论了其潜在机制。
