SELENOPROTEIN T MIMETIC, PSELT, AMELIORATES BEHAVIORAL ALTERATIONS AND OXIDATIVE STRESS IN A PRENATAL VALPROIC ACID MOUSE MODEL OF AUTISM

Prenatal exposure to valproic acid (VPA) is a well-established animal model of autism spectrum disorder (ASD), widely used to investigate neurodevelopmental alterations associated with the disorder. Accumulating evidence indicates that oxidative stress plays a central role in mediating the neuropathological and behavioral phenotypes observed in ASD. Selenoprotein T, an endoplasmic reticulum–associated selenoprotein with redox-regulatory properties, has emerged as a potential neuroprotective factor; however, its effects in ASD-relevant models remain largely unexplored. In the present study, we examined the effect of a small peptide encompassing the redox-active site of selenoprotein T (PSELT) in a prenatal VPA mouse model of ASD, focusing on behavioral performance and hippocampal oxidative status. Offspring prenatally exposed to VPA exhibited hallmark ASD-like behaviors, including increased stereotyped and repetitive behaviors and impaired social interactions. These behavioral alterations were accompanied by elevated hippocampal oxidative stress, consistent with previous reports linking redox imbalance to ASD phenotypes. PSELT administration significantly improved behavioral outcomes in VPA-exposed animals and attenuated hippocampal oxidative stress. Collectively, these findings identify PSELT as a promising therapeutic candidate capable of mitigating ASD-like behavioral deficits through modulation of oxidative dysregulation induced by prenatal VPA exposure.