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Role of brain masculinization in the development of autism-related behaviors in animals prenatally exposed to valproic acid

Macarena Varela

  • CABA,
  • Argentina
  • Macarena Varela ¹
  • , Araceli Seiffe ¹𝄒²
  • , Amaicha Mara Depino ¹𝄒³
  • 1 CONICET-Universidad de Buenos Aires, Instituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE), Buenos Aires, Argentina.
  • 2 Universidad de Buenos Aires, Facultad de Ciencias Exactas y Naturales, Departamento de Fisiología, Biología Molecular y Celular, C1428EHA, Buenos Aires, Argentina.
  • 3 Universidad de Buenos Aires, Facultad de Ciencias Exactas y Naturales, Departamento de Biodiversidad y Biología Experimental, Buenos Aires, Argentina.

Autism Spectrum Disorder(ASD) is characterized by social deficits and fixed or repetitive behaviors. Epidemiological data shows that ASD affects men and women in a proportion of 4:1, which could indicate higher male susceptibility and/or female resilience. Studying the causes of male prevalence of ASD could help determine its etiology as well as identify potential therapeutic targets.
Aiming to understand the biology behind male susceptibility and/or female resilience to ASD, we hypothesize that brain masculinization is necessary for the expression of ASD related behaviors in a prenatal valproic acid(VPA) exposure model. Prenatal VPA exposure results in social deficits, increased fixed or repetitive behaviors and neuroinflammation. Male rodents go through a perinatal brain masculinization process characterized by testosterone aromatization into estradiol which results in adult male sexual behaviors.
This project combines both models(VPA and brain masculinization) via prenatal and postnatal mice treatment. On gestational day 12.5, pregnant dams will be injected with either VPA or saline. On days 2,5 and 8 female offspring will be injected with either estradiol or oil. Behavioral tests will be analyzed to study the effects of female brain masculinization on ASD related behaviors of prenatally exposed VPA mice. Tissue will be obtained for histological and molecular testing to study cellular and molecular alterations mediating VPA and masculinization effects on female behavior.