N-acetylcysteine ameliorates repetitive/stereotypic behavior due to its antioxidant properties without activation of the canonical Wnt pathway in a valproic acid-induced rat model of autism

N-acetylcysteine (NAC) is widely used as an antioxidant, and previous studies have suggested that it may have potential as an alternative therapeutic strategy for the treatment of patients with autism. However, the exact effects of NAC administration on the development of autism, as well as the molecular mechanisms underlying its actions, have yet to be fully elucidated. The present study aimed to investigate the effects of NAC on the oxidative status of rats in a valproic acid (VPA)-induced model of autism, and to examine the involvement of the canonical Wnt signaling pathway in the actions of NAC. Rats exposed to VPA were monitored for behavioral changes, and oxidative stress indicators and key molecules of the canonical Wnt pathway were investigated using colorimetric and western blot analysis, respectively. The present results demonstrated that NAC ameliorated repetitive and stereotypic activity in autism model rats. Furthermore, NAC was revealed to relieve oxidative stress, as demonstrated by the increased glutathione and reduced malondialdehyde levels compared with VPA-treated rats. However, NAC did not appear to affect the activity of the canonical Wnt signaling pathway. The present findings suggested that the beneficial effects of NAC in autism may be associated with its antioxidative properties, and may not be mediated by the canonical Wnt pathway. However, it may be hypothesized that the canonical Wnt pathway can be indirectly regulated by NAC through the activation of other signaling pathways or upstream factors. Taken together, the present study has contributed to the elucidation of the molecular mechanisms that underlie the actions of NAC in autism, suggesting its potential for the development of novel therapeutic strategies for the treatment of patients with autism.