Social rescue of autism-related symptoms in a mouse model

CAMPOLONGO M; KAZLAUSKAS N; LUCCHINA L; DEPINO A

Buenos AIres

Congreso; 5th Special Conference of the International Society for Neurochemistry: Synapses and Dedritic Spines in Health and Disease; 2012

International Society for Neurochemistry

Autism is a severe neurodevelopmental disorder characterized by impediments in social interaction, a reduction in communicative skills and by stereotyped or restricted behaviors. Although symptoms of autism tend to last the entire life, clinical studies have reported that the most effective treatment to date is through intensive behavioral interventions. Autistic children show significant improvements in social behavior through these approaches. To identify the cellular and molecular mechanisms that mediate this social rescue, we first validated a mouse model of autism. In the CF1 outbred strain, the prenatal exposure at gestational day 12.5 to valproic acid (VPA) resulted in reduced social interaction in the adult offspring along with other autism-related phenotypes. As was previously reported, VPA-treated mice are weaned with other VPA mice in these experiments. To evaluate the social contribution to this phenotype, VPA mice were weaned in VPA only (VPA-VPA mice) or VPA-Saline groups (VPA-Sal or Sal-VPA), containing 2-3 VPA-treated mice per cage along with 2-3 Saline-treated mice. Mice interacted from postnatal day (P)21 to P60 in their homecage. At P60, VPA-VPA mice showed a behavioral phenotype related to autism, but in VPA-Sal mice this phenotype was attenuated. Our results show then that this treatment can rescue some symptoms of the autism-related phenotype in our model. Moreover, they give predictive validity to this model, showing that an effective treatment for patients can also have a similar effect in our mouse model. Using this animal model, we are studying what are the cellular and molecular changes that correlate with the autism-related phenotype and whether these or other pathways participate in the social rescue that we observe. To this aim, we are studying the inflammatory alterations in these mice (as we have previously found that VPA-treated mice have increased inflammatory response in adulthood), and we are characterizing the neuronal activation observed upon exposure to a novel object or to a social novelty.