Effects of sulindac on oxidative stress in an autistic model induced by pre-natal exposure to valproic acid / 中国病理生理杂志

ABSTRACT

[ ABSTRACT] AIM:To investigate the effects of sulindac on oxidative stress in autism.METHODS:With an au-tistic model induced by prenatal exposure to valproic acid ( VPA) , we detected the expression of the signaling molecules of canonical Wnt pathway in the prefrontal cortex ( PFC) and hippocampus ( HC) of autistic rats treated with sulindac.The protein expression levels of glycogen synthase kinase 3β(GSK-3β), β-catenin and 4-hydroxynonenal (4-HNE) were ob-served by Western blotting.The mRNA expression of thioredoxin(Trx)1 and Trx2 was assessed by semi-quantitative RT-PCR.RESULTS:The protein level of GSK-3βand mRNA levels of Trx1 and Trx2 were lower, whereas the protein expres-sion levels ofβ-catenin and 4-HNE were higher in VPA group than those in control group.In contrast, the protein levels of GSK-3βwere significantly higher in the animals treated with both VPA and sulindac than those in VPA group, while the lev-els ofβ-catenin and 4-HNE were decreased.CONCLUSION:Sulindac attenuates oxidative stress in the pathogenesis of au-tism, suggesting the up-regulation of the Wnt/β-catenin signaling pathway disrupts oxidative homeostasis and further facili-tates susceptibility to autism.