Effect of lipopolysaccharide exposure on neuro-immune system of rat offspring with autism spectrum disorder at second trimester

Abstract

Objective To establish the lipopolysaccharide(LPS)-induced autism spectrum disorder(ASD) models at second trimester in rat offspring, and to investigate the effect of LPS exposure on social interaction behavior and neuro-immune system in rat offspring. Methods Twelve-week-old pregnant specific pathogen free rats were randomly divided into non-exposed group(10 cases) and LPS-exposed group(10 cases). Rats in the exposure group were intraperitoneally injected with LPS 25 mg/kg at 12.5 d, while rats in the non-exposed group were intraperitoneally injected with 9 g/L saline.At the age of 28 days, 10 rats were randomly selected from each group as the experimental group and the control group.The following tests were carried out in two groups of rats.Their offspring were randomly allocated to the control group (10 cases) and the experimental group (10 cases). The autism-like social behaviors were evaluated by the social interaction test.Density of dendritic spine was analyzed by Golgi staining.The expression of glial fibrillary acidic protein (GFAP) and ionized calcium-binding adapter molecule 1(IBA1) were analyzed by immunohistochemisty.The levels of interleukin(IL)-1β, IL-4, IL-6, IL-10, interferon-gamma(IFN-γ), and transforming growth factor-beta(TGF-β) in rat offspring were detected by enzyme-linked immunosorbent assay. Results The score of social interaction test in the experimental group [(-197.81±101.83) scores] was lower than that in the control group [(132.73±114.63) scores], and the difference was statistically significant (t=5.453, P<0.05). Density of dendritic spine in CA1 region of hippocampus was lower in the experimental group[(7.71±1.33) numbers/10 μm] than that in the control group[(9.66±1.76) numbers/10 μm] by Golgi staining, and the difference was statistically significant(t=2.775, P<0.05). Expressions of GFAP and IBA1 in experimental group were higher than those in the control group by immunohistochemisty.Levels of IL-1β, IL-6, IL-10 and IFN-γ in the experimental group were higher than those in the control group, while level of TGF-β was lower than that in the control group, and the differences were statistically significant(all P<0.05). The scores of social interaction test were correlated with the levels of IFN-γ(r=0.756, P<0.05). Conclusion LPS exposure at early pregnancy may affect the neuro-immune system of rat offspring and result in autism-like behavior. Key words: Lipopolysaccharide; Autism spectrum disorder; Cytokines; Neuro-immune system