丝裂酶原活化蛋白激酶(Mitogen-activated protein kinase,MAPK)是生物体内重要的信号转导通路之一,主要有ERK、p38和JNK三条途径,参与调控多种细胞应答和生理病理过程。ERK和p38在神经损伤的区域迅速激活,减少神经损伤对机体带来的影响;磷酸化JNK在神经损伤部位聚集,促进神经细胞的凋亡,加重神经损伤发生的过程。MAPK信号通路与神经系统损伤的发生。
The purpose of the study was to investigate the impact of rat cytomegalovirus （RCMV） infection on the development of the nervous system in rat embryos, and to evaluate the involvement of Wnt signaling pathway key molecules and the downstream gene neurogenin 1 （Ngnl） in RCMV infected neural stem cells （NSCs）. Infection and control groups were established, each containing 20 pregnant Wistar rats. Rats in the infection group were inoculated with RCMV by intraperitoneal injection on the first day of pregnancy. Rat E20 embryos were taken to evaluate the teratogenic rate. NSCs were isolated from El3 embryos, and maintained in vitro. We found： 1） Poor fetal development was found in the infection group with low survival and high malformation rates. 2） The proliferation and differentiation of NSCs were affected. In the infection group, NSCs proliferated more slowly and had a lower neurosphere formation rate than the control. The differentiation ratio from NSCs to neurons and glial cells was significantly different from that of the control, showed by immunofluorescenee staining. 3） Ngnl mRNA expression and the nuclear p-catenin protein level were significantly lower than the control on day 2 when NSCs differentiated. 4） The Morris water maze test was performed on 4-week pups, and the infected rats were found worse in learning and memory ability. In a summary, RCMV infection caused abnormalities in the rat embryonic nervous system, significantly inhibited NSC proliferation and differentiation, and inhibited the expression of key molecules in the Wnt/β-catenin signaling pathway so as to affect NSCs differentiation. This may be an important mechanism by which RCMV causes embryonic nervous system abnormalities.
Xiuning SunYingJun GuanFengjie LiXutong LiXiaowen WangZhiyu GuanKai ShengLi YuZhijun Liu
目的探讨高温致神经管畸形(neural tube defects,NTD)的分子机制,为防治NTD的发生提供理论依据。方法在高温致金黄地鼠NTD模型的基础上,应用Western blot技术和免疫荧光染色技术观察NTD发生过程中转录抑制因子(Hairy and enhancer of split homolog-1,Hes1)在鼠胚神经上皮细胞中的表达变化。结果 Western blot结果显示:Hes1蛋白在正常对照组金黄地鼠神经管中稳定表达。高温后Hes1的表达有不同程度的降低,其中高温后16h、36h(即E8.5﹑E9.5)与正常对照组相比差异有统计学意义(P<0.05)。Hes1免疫阳性产物主要分布于鼠胚神经管上皮细胞和周围间充质细胞的胞浆中,高温后不同时间点胚胎神经上皮细胞内的Hes1表达量较对照组减弱。其中高温处理后16h、36h(即E8.5﹑E9.5)差异显著(P<0.05)。结论 Hes1参与了胚胎神经管的发育过程,其表达降低在NTD的发生中起重要作用。
