Effects of rat cytomegalovirus on the nervous system of the early rat embryo.
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 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 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.
Department of Parasitology, Weifang Medical University, Weifang, 261000, China.
Xiuning
X
Sun
YingJun
Y
Guan
Fengjie
F
Li
Xutong
X
Li
Xiaowen
X
Wang
Zhiyu
Z
Guan
Kai
K
Sheng
Li
L
Yu
Zhijun
Z
Liu
D000818:Animals; D000831:Animals, Newborn; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D005260:Female; D008297:Male; D018146:Muromegalovirus / Q000472:pathogenicity*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009420:Nervous System / Q000821:virology*; D009422:Nervous System Diseases / Q000473:pathology / Q000821:virology; D058953:Neural Stem Cells / Q000502:physiology / Q000821:virology; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D016019:Survival Analysis; D060449:Wnt Signaling Pathway
D051792:Basic Helix-Loop-Helix Proteins; D009419:Nerve Tissue Proteins; C510879:neurogenin-1, rat