Impaired spatial learning and memory skill in Sprauge-Dawley rat model of congenital human cytomegalovirus infection

Abstract

Objective To investigate the influence of congenital human cytomegalovirus (HCMV) infection on spatial learning and memory skill in rats and its mechanism. Methods Forty specific pathogen free Sprague-Dawley rats (12 weeks old, male and female mated by 1∶3) were selected and randomly divided into the experimental group and control group, fifteen in each group. Fertilized female rats in the experimental group were injected with 0.5 ml HCMV (1×10-6 of the 50% tissue culture infective dose/rat) by intraperitoneal inoculation on the third gestational day. At the same time, a 0.5 ml suspension of human embryonic lung fibroblast cells was inoculated intraperitoneally into fertilized female rats in the control group. HCMV-specific IgM and IgG in maternal peripheral blood of the two groups were detected on one week after inoculation. Both side of hippocampus of ten neonatal rats (five in each group), born by cesarean section, were collected for virus isolation. Spatial learning and memory skill in 4-6 week offspring in the two groups were assessed using the Morris Water Maze (MWM) test, and results were presented by Origin 8.0. Pathological damage in offspring was determined by microscopy and electron microscopy. Independent samples t-test, Chi-square and rank sum tests were used for statistical analysis. Results (1) Compared with the control group, litter size and mortality of neonatal rats within one week after birth in the experimental group were significantly higher [litter size: (8.7±3.1) vs (5.5±2.4), t=2.366, P=0.033; mortality of neonatal rats: 4.9% (6/122) vs 26.1% (18/69), χ2=191.020, P=0.000. In the MWM test, escape latency in 30-day old offspring in the experimental group was significantly increased compared with the control group during 4 days of training (F=499.473, P=0.000). The total distance in the experimental group was significantly increased compared with the control group (F=440.167, P=0.000). In addition, the numbers of platform crossing (4.21±1.44) and swimming time in the target quadrant [(26±4)%] in the congenital infection group were decreased compared with the control group [(7.50±1.72) and (47±5)%, t=7.182 and 15.487, P=0.003 and 0.000]. In the congenital infection group, liquefaction necrosis of the cerebral cortex (light microscopy) and myelin disintegration in the hippocampus (electron microscopy) were observed. Conclusions Injury of the cortex and hippocampus in offspring with congenital HCMV infection is involved in the pathological mechanism of decreased spatial learning and memory skill. Key words: Pregnancy complications, infectious; Cytomegalovirus infections; Hippocampus; Learning; Memory; Disease models, animal