Abstract
Autism is a neurodevelopmental disorder characterized by qualitative impairment in communication, social interaction, and repetitive stereotypic behavior. Resveratrol plays a role in several disorders such as neu- roimmune, autoimmune, and allergic disorders. BTBR T+ Itpr3(tf)/J (BTBR) mice, a model for autism, show several behavioral deficits that are physiological characteristics similar to those observed in patients with autism. Previous studies have shown that JAK-STAT signaling pathway is associated with many neurodevelopmental disorders. We investigated the possible role of resveratrol on IL-6(+), TNF-alpha(+), IFN-gamma(+), and STAT3(+) in CD4(+) T spleen cells in BTBR mice as compared to C57BL/6J mice. We also assessed the effect of resveratrol treatment on IL-6, TNF-alpha, IFN-gamma, JAK1, and STAT3 mRNA expression levels in the brain tissue. We further assessed IL-6, IFN-gamma, TNF-alpha, phosphorylated (p) JAK1, and pSTAT3 (Tyr705) protein expression levels in the brain tissue. Resveratrol (20 and 40 mg/kg)-treated mice had significantly decreased in IL-6(+), TNF-alpha(+), IFN-gamma(+), and STAT3(+) in CD4(+) spleen cells as compared with BTBR control mice. Resveratrol treatment also decreased IL-6, TNF-alpha, IFN-gamma, JAK1, and STAT3 mRNA expression levels as compared with BTBR control mice in the brain tissue. Moreover, resveratrol treatment resulted in decreased protein expression levels of IL-6, IFN-gamma, TNF-alpha, pJAK1, and pSTAT3 (Tyr705) as compared with BTBR control mice in the brain tissues. Taken together, these results indicate the efficacy of resveratrol in reducing cytokines and JAK-1/STAT3 signaling in BTBR mice, which is a novel and important finding and might be important for future therapies in neuroimmune dysfunction.