The modelling of the autism spectrum disorder of Sprague-Dawley rat exposed to Poly-IC in the pregnancy and the preliminary study of neuropathologic changes

Abstract

Objective Through modelling autism spectrum disorder(ASD) in condition of Poly-IC, to analyze the development, nervous pathological changes and behavior of rats in experiments, and to define whether the Sprague-Dawley(SD) rats are suitable for the study of ASD. Methods Ten SD rats were randomly divided in 2 groups with 5 rats in each group.The experimental group rats were injected intraperitoneally with 5 mg/kg Poly-IC at gestational day 12, while the rats in control group were injected intraperitoneally with 9 g/L normal saline at the gestational day 12.The body weight, eye-opening time, swimming performance, and conduct parallel water maze test, social communication ability test of each offspring were recorded, and the developmental state of rats and the existence of autism-like social behavior were evaluated.The alterations in hippocampus morphology of offspring rats were indirectly observed with immunofluorescence double standard dyeing. Results Compared with the control group, the weights of the experimental rats were lighter, opening-eye time was delayed, swimming score was lower, in each measurement point.The differences above all were significant(all P<0.05). The near-escape scores of experiment rats in social communication ability test were lower than those of rats in control group.The rats in the experimental group needed more time to get the Morris water maze platform, and the times of rightly run through the Morris water maze decreased significantly, and the differences were significant(all P<0.05). Pathological results revealed that the mineralocorticoid receptor(MR)average optical density value (0.061 3±0.028 8) and the glucocorticoid receptor(GR)mean optical density value (0.041 9±0.040 3) in hippocampal CA1 area of experiment rats were lower than those of the control group(MR: 0.081 3±0.053 9; GR: 0.061 2±0.043 6)(t=10.319, 10.241; all P<0.05). There was no significant diffe-rence between MR/GR ratio(the ratio of MR and GR optical density value in the same vision area) in experimental group and in the control group. Conclusions The Poly-IC during early pregnancy can cause lag behind in motor development, harm the social communication ability, lose memory ability to learn, and develop ASD symptoms of SD rat, and these symptoms may be associated with abnormal expression of MR and GR on the hippo-camp cells surface.AS a consequence, early pregnant SD rats exposed to Poly-IC can be used for the establishment of the model of ASD which can provide a platform for the research of ASD. Key words: Autism spectrum disorder; Model; Rat; Neurobehavioral manifestations; Poly-IC