Environmental enrichment intervention in the VPAS rat model of autism: impact on behavioral impairments and long-distance tract myelination

UCCELLI NONTHUE; CODAGNONE MARTIN; TRAETTA MARIANELA; ROSATO SIRI MARÍA VICTORIA; MOLINA MANUEL; ZÁRATE SANDRA; PASQUINI JUANA; REINÉS ANALÍA

Simposio; The role of Glia in Health and Disease of the Nervous System: Clinical and Basic Science Walking Together; 2017

Autism Spectrum Disorders (ASD) are neurodevelopmental disorders characterized by connectivity alterations accompanied with neuroinflammation. We reported altered connectivity and reactive gliosis in the valproic acid (VPA) rat model of ASD. Environmental enrichment (EE) is known to alleviate behaviour and influence brain processes as myelination. The aim of this work was to study the corpus callosum (CC) of VPA animals and evaluate behavioural and structural effects of EE. At weaning, VPA or control male rats were housed in standard or EE conditions (CS/VS/CEE/VEE). Behavioural evaluation included maturation parameters (PND7-16) and exploratory and social tests (PND30-35). On PND36, CC expression of myelin basic protein (MBP) and markers for glial cells (Tomato lectin, GFAP, PDGFαR, CC1) were evaluated. Myelin structure was studied by electron microscopy (EM). VS and VEE animals showed delay growth and maturation compared to CS group. At PND30-35, hole pocking number and social exploration index were decreased in VS animals, but reach CS values in the VEE group. VPA rats evidenced lower MBP expression, decreased number of CC1+OL and increased PDGFαR+OL but no changes in microglia or astrocytes levels. EM revealed lower percentage of myelinated axons and aberrant myelin in CC from VPA animals; both ameliorated in VEE. Our results indicate that defective OL maturation could contribute to myelin defects seen in VPA rats and that EE prevents behavioural impairments in pre-pubertal VPA animals as well as the CC structural myelin alterations.