Peer-rescue of autism-related behavior after prenatal exposure to valproic acid

CAMPOLONGO, MARCOS; KAZLAUSKAS, NADIA; DEPINO, AMAICHA

Vancouver

Congreso; 9TH Annual Canadian Neuroscience Meeting 2015; 2015

Autism is a severe neurodevelopmental disorder characterized by impediments in socialinteraction, a reduction in communicative skills and by stereotyped or restricted behaviors.Symptoms appear in early childhood and persist in adulthood. Currently there are nopharmacological treatments, but several clinical studies suggest early social stimulation as themost effective treatment of autistic children, who show significant improvements in socialbehavior through these approaches.Our aim is to analyze the effects of early social stimulation on autism-related behavior and itsconsequences in molecular and cellular pathways that could be altered in autism.It was previously shown that the mouse prenatal exposure to valproic acid (VPA) at gestationalday 12.5 results in reduced social interaction in the adult offspring. In those experiments VPAtreatedmice were weaned with other VPA mice.Here, we compared VPA mice weaned with VPA mice (VPA-VPA mice) with VPA-Saline groups(VPA-Sal), containing 2-3 VPA-exposed mice per cage along with 2-3 Saline mice. This designallowed VPA and Sal mice to interact in the home cage from postnatal day (P)21 to P60. AtP60, VPA-Sal mice showed higher levels of sociability than VPA-VPA, showing that thistreatment can rescue at least some of the behavioral alterations observed in our model.On the other hand, there are evidences to suggest that patients with autism have alterations instress and inflammatory responses. We have previously identified alterations in inflammatoryand stress response after inflammatory stimuli in VPA mice. We therefore studied whetherthese alterations are reversed in rescued animals. In addition, given that changes on socialbehavior by social stimulation, we also evaluated the effect of social novelty on the stressresponse.