Peers can rescue autism-related behaviors after prenatal exposure to valproic acid: Role of the piriform cortex

DEPINO AM; CAMPOLONGO M; KAZLAUSKAS N; FALASCO G; URRUTIA L; SALGUEIRO N

Washington DC

Congreso; 2017 Society for Neuroscience Meeting; 2017

Society for Neuroscience

Autism spectrum disorder is characterized by poor social interaction. Symptoms appear in early life and persist in adulthood. Early social stimulation can help revert some of the symptoms, but the biological mechanisms of action are unknown. Our aim was to analyze the effects of early social stimulation on autism-related behavior in the mouse and its consequences on brain function. To this aim, we exposed mice to valproic acid (VPA) at gestational day 12.5. We show that these mice play less as juveniles and, when reared with other VPA mice, they perform less social interaction in adulthood. However, when VPA animals were caged with control animals between postnatal day (PD) 21 to PD60, this behavioral alteration was rescued. Interestingly, repetitive behaviors (time in self-grooming, and arm alternation in the Y-maze) and depression-related behaviors (immobility in tail suspension and forced swim tests) were not affected by this protocol of social enrichment. Moreover, anxiety related behaviors assayed in either the elevated plus maze, the open field, and the dark/light box were not affected by either the prenatal or the postnatal treatment. We then used [18F]-FDG preclinical PET imaging for an unbiased analysis of the whole brain of these mice, and found that VPA animals present high levels of metabolism in basal conditions, mainly in the piriform cortex (Pir), a region involved in social behavior in mice. Remarkably, this effect was reversed after social stimulation. In addition, we found increased dopamine turnover in the Pir in VPA-VPA mice, which is normalized in peer-rescued animals. Finallly, we evaluated the activation of the Pir in response to novel social stimuli, in all our experimental groups.