CONICET | Buscador de Institutos y Recursos Humanos

Autism spectrum disorders (ASD) are characterized by reduced sociability, diminished communicative skills and repetitive behaviors. Notably, the proportion between boys and girls diagnosed with ASD is about 4:1. To identify the biological mechanisms involved in this bias, we use a mouse model of ASD: the prenatal exposure to valproic acid (VPA). Recently, we observed that this model also presents a different phenotype in males and females, as females do not show the reduction in sociability observed in adult males. Our hypothesis is that the masculinization process that male brains experience during development is necessary for VPA prenatal exposure to affect autism-related behaviors, neuronal alterations and gliosis.To test this hypothesis, we study the effect of brain masculinization of female mice on the VPA model. In rodents, normal masculinization of some brain regions involves inflammatory signaling molecules. At the same time, a striking risk factor for ASD corresponds to deregulations of the immune system. So, the natural process of masculinization increases inflammation in males and pushes males closer to a threshold of vulnerability that can be more easily reached if inflammation occurs during a sensitive developmental period. We hypothesize that VPA female mice will show impaired sociability after a masculinization protocol. Our preliminary experiments demonstrate indeed that masculinized VPA females show alterations in sociability.

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