Effects of environmental enrichment on oligodendrocyte differentiation and myelin ultrastructure in an experimental model of autism spectrum disorders

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

Congreso; ASN 2018; 2018

Autism Spectrum Disorders are characterized by social and communication deficits and impaired brain connectivity. Based on functional imaging studies, it has been proposed the hyper-connectivity of local microcircuits and the long-distance tract hypo-connectivity hypothesis. Environmental enrichment (EE) is a therapeutic strategy known to alleviate behavioural deficits and to modulate brain function. The aim of this work was to study the structure of the corpus callosum (CC) of rats prenatally exposed to valproic acid (VPA) and evaluate the behavioural and molecular effects of EE interventions. Pregnant Wistar rats were administrated with VPA (450mg/kg) or saline on gestation day 10.5. On early and juvenile stages, behavioural validation of the VPA phenotype was carried out. At weaning, male pups from both groups were housed in standard or enriched conditions. In the CC of VPA rats, the number of mature oligodendrocytes (CC1+ cells) diminished while the number of immature oligodendrocytes (PDGF+ cells) increased when compared with controls. These alterations were observed in the absence of astrogliosis (GFAP immunolabelling) or microgliosis (Tomato lectin labelling). Concomitantly, myelin basic protein expression levels were reduced in the CC of VPA rats. By electron microscopy, aberrant myelin sheet ultrastructure and decreased density of myelinated axons were also found in the CC of VPA rats. EE intervention fully prevented myelin ultrastructure alterations as well as the impairments in exploratory activity and social exploration seen in VPA animals. Our results suggest that CC myelin defects in VPA rats could be related to altered oligodendrocyte maturation and that, its prevention by EE could be due to an experience-dependent modulation of olygodendrocyte fate.