CONICET | Buscador de Institutos y Recursos Humanos

Autism Spectrum Disorders (ASD) are characterized by behavioural and connectivity alterations accompanied with neuroinflammation. We previously reported evidences supporting the short-distance hyperconnectivity hypothesis in the valproic acid (VPA) rat model of ASD. Experiences as environmental enrichment (EE) are known to alleviate behavioural impairments and influence brain processes. The aim of this work was to study long-distance connectivity in the corpus callosum (CC) of VPA animals and evaluate behavioural and structural effects of EE. VPA or control male rats were weaned on postnatal day (PND)21 and housed in two conditions: standard or EE. Behavioural evaluation was performed at PND7-16 (maturation parameters) and PND30-35 (exploratory activity and social test). On PND36, CC expression of myelin basic protein (MBP) and markers for microglia (Tomato lectin labelling), astrocytes (GFAP) and mature (CC1) and immature (PDGFαR) oligodendrocytes (OL) were evaluated. Myelin structure was studied in all groups (CS/VS/CEE/VEE) by electron microscopy (EM). At PND7-16, VS and VEE animals showed similar growth and maturation, delay in comparison with the CS group. At PND30-35, while hole pocking number and social exploration index were decreased in the VS group, exploratory and social behaviours in the VEE group did not differ from CS. VPA rats evidenced lower MBP expression, decreased number of CC1+OL and increased PDGFαR+OL but no changes in tomato lectin or GFAP levels. EM of CC from VPA animals revealed lower percentage of myelinated axons and aberrant myelin; both myelin alterations were ameliorated in VEE animals. Our results indicate that defective OL maturation could contribute to myelin defects seen in VPA animals. EE can prevent the behavioural impairment seen in pre-pubertal stage of VPA animals as well as the structural myelin alterations observed in the CC of VPA group.