OBJECTIVE: To investigate the effect of sulindac on the symptoms and behaviors of autism model rats.
Method: A one-time intraperitoneal injection of sodium valproate (VPA) was used to prepare autism rat model after 12.5 days of pregnancy. For the sulindac treatment group, rats were orally administered 20 mg/kg sulindac every day after VPA injection until weaning. The newborn rats were divided into 4 groups: control group, VPA treatment group, sulindac treatment group and VPA combined sulindac treatment group. At 35 days after birth, the young mice were tested for social interaction behaviors, open-box anxiety-like behaviors, and separated and extracted brain tissue proteins. Western blot was used to analyze the expression of key proteins β-catenin and Gsk3β in the Wnt signaling pathway.
Result: A rat model of autism was successfully prepared. Compared with the control group, the VPA treatment group has decreased social communication ability, increased activity time in the central area, and reduced the number of standing, which is consistent with the behavioral characteristics of autism; sulindac alone treatment group has no obvious behavioral changes; but sulindac combined treatment can Significantly improve the behavioral symptoms of autism caused by VPA treatment. Western blot results show that compared with the control group, VPA treatment can increase the expression of β-catenin in the prefrontal lobe, hippocampus and cerebellum of rats and reduce the phosphorylation level of Serine 9 of Gsk3β; while the combined treatment of sulindac can inhibit The expression level of β-catenin in the above-mentioned brain tissues increases the phosphorylation level of Serine 9 of Gsk3β.
Conclusion: Sulindac can improve the behavior of autism model rats, the mechanism may be related to the inhibition of Wnt signaling pathway in brain tissue.