Avaliação dos efeitos preventivos do trans-resveratrol administrado durante a gestação sobre parâmetros comportamentais e oxidativos na prole de camundongos Swiss submetida à exposição pré-natal ao ácido valproico

Abstract

Autism Spectrum Disorder (ASD) is a neurodevelopmental disordercharacterized by persistent deficits in social communication and social interaction, as well as restricted and repetitive patterns of behavior. Experimental and clinical evidence indicates that ASD is associated with cognitive impairments, neuroinflammatory processes, and imbalance of the cerebral redox system. Valproic acid (VPA) is widely used as an experimental model because it mimics behavioral and neurobiological alterations observed in ASD. In this context, trans-resveratrol, a natural polyphenol with well-established antioxidant and anti-inflammatory properties, has been investigated for its potential neuroprotective and preventive effects during critical periods of neurodevelopment. The aim of this study was to evaluate the preventive effects of trans-resveratrol on memory and cerebral oxidative stress in mice using the VPA-induced ASD model. Pregnant females received VPA (450 mg/kg, intraperitoneally, on gestational day 12.5) to induce an ASD-like phenotype and were concomitantly treated with trans-resveratrol (30 mg/kg/day, intraperitoneally) throughout the gestational period. Offspring were subjected to the Y-maze test to assess working memory, and subsequently, levels of reduced glutathione (GSH), malondialdehyde (MDA), and total proteins were quantified in the prefrontal cortex and hippocampus. The results demonstrated that male offspring exposed to VPA and born to females treated with trans-resveratrol showed improved memory performance (N = 4), an effect not observed in females (N = 6). In addition, increased GSH levels were observed in both sexes and in both brain regions analyzed, indicating enhancement of antioxidant defenses. MDA levels were increased in the prefrontal cortex of VPA-exposed males compared to the control group (control males, N = 11; VPA males, N = 8), whereas trans-resveratrol treatment reduced these levels in both the prefrontal cortex and hippocampus. In females, MDA levels were higher in the VPA group compared to controls (control females, N = 10; VPA females, N = 16), with a reduction observed only in the prefrontal cortex following trans-resveratrol treatment. No differences were observed in total protein quantification among the experimental groups. Taken together, these findings suggest that trans-resveratrol exerts a neuroprotective effect through modulation of oxidative stress, contributing to improved memory performance in males and reinforcing its potential as a preventive strategy in the context of ASD.