ENVIRONMENTAL ENRICHMENT PREVENTS BEHAVIORAL AND CONNECTIVIT Y ALTERATIONS IN AN EXPERIMENTAL MODEL OF AUTISM SPECTRUM DISORDERS

UCCELLI NA; TRAETTA M; URRUTIA L; PASQUINI J; LEVANOVICH N; LACOUR JV; VAZQUEZ S; CODAGNONE M; ROSATO SIRI MV; FALASCO G; REINÉS A

Mar del Plata

Congreso; LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC).; 2019

Sociedad Argentina de Investigación Clínica (SAIC).

Autism spectrum disorders (ASD) are a group of neurodevelopmental disabilities characterized by social impairments and atypical connectivity. Studies in patients report hypo- and hyper-connectivity and alterations in the corpus callosum (CC), the main structure that connects brain hemispheres. No pharmacological approaches for ASD core symptoms are available and behavioural therapies have shown the best outcomes. The aim of this work was to study brain connectivity in a rat model of ASD and evaluate benefits of environmental enrichment, dissecting the role of social and physical stimuli. For this purpose, pregnant dams were administrated with valproic acid (VPA) or saline and behavioural, functional (PET), ultrastructural and molecular parameters were studied in male pups. VPA animals showed delayed growth, maturation and behavioural development in early stages. Pups were weaned and kept in standard (S), physically plus socially (EE) or physically (PE) enriched environments. In juvenile stages, VPA rats exhibited decreased exploratory activity and sociability. PET showed lower global glucose uptake in VPA brain with greater uptake in local areas related with core symptoms. CC from VPA rats elicited diminished percentage of myelinated axons and Gratio. Oligodendrocyte lineage was explored: CC1+ cells decreased and PDGFR+ cells increased in the CC of VPA rats. EE fully prevented behavioural and ultrastructural deficits in juvenile VPA rats and had partial effects on cellular changes. PE had the same behavioural benefits than EE. This work demonstrates brain metabolic alterations in VPA rats that can be related with connectivity deficits. Also, aberrant myelin ultrastructure and alterations in oligodendroglia support the long-distance hypoconnectivity hypothesis for ASD. Our results indicate that social stimulus is not necessary to provide behavioural benefits in VPA rats and postulate PE and EE as valuable tools for the development of therapeutic strategies in ASD.