Sex-specific alterations in behavior and neuroinflammation in a mouse model of autism

DEPINO AMAICHA; ZAPPALA CECILIA; KAZLAUSKAS NADIA; CAMPOLONGO MARCOS

Daegu

Congreso; International Brain Research Organization (IBRO) World Congress of Neuroscience; 2019

International Brain Research Organization (IBRO) World Congress of Neuroscience

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with an incidencethree times higher in boys than in girls. By analyzing the effect of sex in a mousemodel of ASD, we were able to identify immune alterations that could underlie this sexbias.Pregnant mice were injected subcutaneously with 600 mg/kg of valproic acid (VPA) orsaline at gestational day 12.5. Their male and female offspring were evaluated in asocial interaction test at adulthood, and only male VPA mice showed reducedsociability levels and a lack of social preference. We then analyzed the hypothalamuspituitary-adrenal (HPA) response and the neuroinaammatory state in adult and younganimals. Adult VPA males exhibited increased basal corticosterone levels, while VPAfemales showed levels comparable to controls. As male mice showed a blunted HPAactivation at PD21 when compared to female mice, we propose that this earlydimorphism could explain the different effects of VPA on HPA function. In addition,prenatal VPA exposure resulted in altered astroglial and microglial cell density levels inthe dentate gyrus and the cerebellum in adult mice. These neuroinaammatory effectswere more pronounced in female than male mice, and appeared at earlydevelopmental stages. We propose that these postnatal glial density differences couldunderlie the behavioral differences observed in adulthood, when only males show a social deficit.We consider that our work contributes to the understanding of biological mechanismsaffected by VPA on male and female rodents, and to shed light on the study of possibleresilience mechanisms in the female population and/or susceptibility to ASD in boys.