Objective: To study the effect of sulindac on the symptoms and behaviors of autism model rats.
Method: Use intraperitoneal injection of sodium valproate (VPA) for 12.5 days of pregnancy to establish a rat model of autism. In the sulindac treatment group, rats were orally given 20 mg/kg sulindac every day after VPA injection until weaning. The newborn rats were divided into four groups: control group, VPA treatment group, sulindac treatment group and sulindac treatment group VPA. On the 35th day of life, the social interaction behavior of young mice, out-of-the-box anxiety-like behavior, and the separation and extraction of brain tissue proteins were tested. Westernblot was used to analyze the expression of major proteins β-catenin and Gsk3β. Wnt signaling pathway.
Result: We have successfully created a rat model of autism. Compared with the control group, the group receiving VPA treatment reduced social communication skills, increased activity time in the central region, and reduced the number of people standing. This is consistent with the behavioral characteristics of autism. There was no obvious behavior change in the sulindac monotherapy group. However, sulindac combination therapy can significantly improve the behavioral symptoms of autism caused by VPA treatment. Westernblot results showed that compared with the control group, VPA treatment may increase the expression of β-catenin in the frontal lobe, hippocampus and cerebellum of rats, and reduce the level of Serine 9 phosphorylation of Gsk3β. It increases the expression level of β-catenin in the above-mentioned brain tissue and the phosphorylation level of Serine 9 of Gsk3β.
Conclusion: Sulindac can improve the behavior of autism model rats. This mechanism may be related to the inhibition of Wnt signaling pathway in brain tissue.