Disorders of the Nervous System
Author: Lucía María Di Guardia Casella | Email: lmdiguardiacasella@gmail.com
Lucía María Di Guardia Casella1°2°, Mariana Elias 1°,Amaicha M. Depino 1°3
1° Instituto de Fisiología, Biología Molecular y Neurociencias (UBA-CONICET)
2° Departamento de Fisiología, Biología Molecular y Celular (FCEN, UBA)
3° Departamento de Biodiversidad y Biología Experimental (FCEN, UBA)
Autism Spectrum Disorder (ASD) is characterized by reduced sociability and increased repetitive behaviors, with a notable male-to-female incidence ratio of 4:1. Previous experiments from our group demonstrated that male mice exposed to valproic acid (VPA) on gestational day 12.5 exhibit reduced sociability at weaning and in adulthood. Interestingly, females prenatally exposed to VPA show sociability alterations before puberty but not in adulthood, indicating that the VPA mouse model is valuable for studying sex differences in ASD behaviors.
Different mechanisms may underlie this juvenile reversal of prenatal VPA effects on social behavior in females . We hypothesized that gonadal hormones may play a role in the observed resilience of females, as ovaries start producing steroids early in the juvenile phase, while testes remain inactive until adulthood. To explore the impact of ovarian hormones on adult behavior, we performed ovariectomy (OVX) in the ASD mouse model at weaning.
Our results revealed that VPA-OVX females did not exhibit the typical preference for the social chamber during the social interaction test, unlike other groups. We also evaluated social recognition, repetitive behaviors, and anxiety- and depression-related behaviors. These findings suggest that the absence of gonadal hormones since prepuberty, a period sensitive to organizational effects by estradiol, may prevent the resilience of female mice to VPA’s impact on sociability later in life.