Effects of Rat Cytomegalovirus on the Nervous System of the Early Rat Embryo
Effects of Rat Cytomegalovirus on the Nervous System of the Early Rat Embryo
复制标题
大鼠巨细胞病毒对早期大鼠胚胎神经系统的影响
DOI：
10.1007/s12250-012-3250-0
复制
发表时间：
2012-08-01
影响因子：
5.5
通讯作者：
Liu, Zhijun
中科院分区：
文献类型：
--
作者：
Sun, Xiuning;Guan, YingJun;Liu, Zhijun
本研究旨在探讨大鼠巨细胞病毒（RCMV）感染对胚胎神经系统发育的影响，以及Wnt信号通路关键分子及其下游基因Neurogenin 1（Ngn 1）在RCMV感染神经干细胞（NSCs）中的作用。建立感染组和对照组，每组20只妊娠Wistar大鼠。感染组大鼠于妊娠第1天腹腔注射RCMV。取大鼠E20胚胎评价致畸率。从E13胚胎中分离神经干细胞，体外培养。结果发现：（1）感染组胎儿发育不良，存活率低，畸形率高; 2)神经干细胞的增殖和分化受到影响。感染组神经干细胞增殖速度慢，神经球形成率低。免疫荧光染色显示，NSCs向神经元和神经胶质细胞分化的比例与对照组相比有显著性差异。3)神经干细胞分化第2天，Ngn 1 mRNA表达和细胞核β-catenin蛋白水平显著低于对照组。4)对4周的幼崽进行莫里斯水迷宫测试，发现感染的大鼠学习记忆能力较差。综上所述，RCMV感染导致大鼠胚胎神经系统异常，显著抑制NSC增殖和分化，抑制Wnt/β-catenin信号通路中关键分子的表达，从而影响NSC分化。这可能是RCMV引起胚胎神经系统异常的重要机制。
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 (Ngn1) 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 E13 embryos, and maintainedin 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 immunofluorescence staining. 3) Ngn1 mRNA expression and the nuclear β-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.