Effect of Valproate exposure-induced autism spectrum disorder model on neuroimmune system of infant mice at early pregnancy
10.3760/cma.j.issn.2095-428X.2015.16.020
- VernacularTitle:孕早期丙戊酸钠暴露对孤独症谱系障碍仔鼠神经免疫系统的影响
- Author:
Jing ZHU
;
Jiulai TANG
- Publication Type:Journal Article
- Keywords:
Autism spectrum disorder;
Cytokines;
Immune dysfunction;
Glial cell;
Social interaction test
- From:
Chinese Journal of Applied Clinical Pediatrics
2015;30(16):1265-1268
- CountryChina
- Language:Chinese
-
Abstract:
Objective To establish the Valproate (VPA) exposure-induced autism spectrum disorder (ASD) model at early pregnancy in rats,and to study the changes of social interaction test and neuroimmune system in autism model rats,and discuss the pathogenic mechanism.Methods Twelve-week-old rats were randomly divided into the non-exposed group (n =10) and the VPA-exposed group (n =10).Their babies were respectively just the normal control group (n =10) and the model group (n =10).The autism-like social behavior was evaluated via the social interaction test.The level of interleukin (IL)-1β,IL-4,IL-6,interferon-gamma (IFN-γ),transforming growth factor-beta (TGF-β) in mothers and offspring were detected by using enzyme-linked immunosorbent assay (ELISA).The histopathological damage in brain was observed with immunohistochemical staining.Results The score of social interaction test in the model group [(-163.16 ± 101.92) scores]was lower than that in the normal control group [(132.73 ± 114.63) scores] (t =-6.100,P ＜ 0.05).The levels of IL-1β,IL-4,IL-6,IFN-γ in VPA-exposed group were higher than those in the non-exposed group (t =5.883,6.394,5.655,5.393,all P ＜ 0.05),while the level of TGF-β was lower than that in the non-exposed group (t =-6.726,P ＜ 0.05).The levels of IL-1β,IL-4,IL-6,IFN-γ in the model group were higher than those in the normal control group(t =3.058,3.048,6.670,5.486,all P ＜ 0.05),while the level of TGF-β was lower than that in the normal control group (t =-6.516,P ＜ 0.05).The change trend of the level of cytokines in the serum of ASD model rats was similar to the change trend of the level of cytokines in the serum of VPA exposed rats.The result of social interaction test the approach-avoidance score was inversely correlated with the levels of IL-1β and IL-4 (r =-0.802,-0.781,all P ＜ 0.05).The result of immunohistochemical staining showed the expressions of glial fibrillary acidic protein (GFAP) and ionized calcium-binding adapter molecule 1 (IBA1) in the model group were higher than those in the normal control group.Conclusions The main neuroimmunological pathogenesis mechanism can be explained as follows:at early pregnancy,the maternal cytokines skewing influenced by VPA exposure can make immune activation,induce immune system dysfunction and affect the brain growth and development,which result in autism-like behavior in offspring.
