Sexual differentiation of the brain as a risk factor in the development of autism-related behaviors

AMAICHA MARA DEPINO

Villa Carlos PAz

Congreso; XXXIV Congreso Anual de la Sociedad Argentina de Investigación en Neurociencias; 2019

Autism Spectrum Disorder (ASD) is characterized by poor social interaction and communication, and the presence of restricted interests and repetitive, stereotyped behaviors. Remarkably, four boys are diagnosed with ASD for every girl, showing a striking male bias in prevalence. Using an animal model of ASD, we are studying the biological processes underlying this higher susceptibility in males and/or the higher resilience in females.Prenatal exposure to valproic acid (VPA) results in adult male mice that interact less with novel social stimuli, exhibit repetitive behaviors and show other behavioral and biological features related with ASD. Interestingly, we found that female offspring prenatally exposed to VPA show normal social behavior, recapitulating what is observed in humans. We then found that exposing females to a second stimulus linked to ASD (postnatal inflammation) results in altered social behavior. These results suggest that female mice are resilient to develop behavioral alterations upon prenatal exposure to VPA.We will finally present some novel hypotheses on the role of the sexual differentiation of the brain as a risk factor for ASD and data supporting this hypothesis.