Environmetal enrichment prevents behavioral impairments and myelin alterations in the VPA experimental model of autism spectrum disorders

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

Congreso; II Reunión Conjunta de Sociedades de Biociencias; 2017

Autism Spectrum Disorders (ASD) are characterized by behaviouraland connectivity alterations accompanied with neuroinflammation.We previously reported evidences supporting theshort-distance hyperconnectivity hypothesis in the valproic acid(VPA) rat model of ASD. Experiences as environmental enrichment(EE) are known to alleviate behavioural impairments and influencebrain processes. The aim of this work was to study long-distanceconnectivity in the corpus callosum (CC) of VPA animals and evaluatebehavioural and structural effects of EE. VPA or control malerats were weaned on postnatal day (PND)21 and housed in twoconditions: standard or EE. Behavioural evaluation was performedat PND7-16 (maturation parameters) and PND30-35 (exploratoryactivity and social test). On PND36, CC expression of myelin basicprotein (MBP) and markers for microglia (Tomato lectin labelling),astrocytes (GFAP) and mature (CC1) and immature (PDGFαR) oligodendrocytes(OL) were evaluated. Myelin structure was studiedin all groups (CS/VS/CEE/VEE) by electron microscopy (EM). AtPND7-16, VS and VEE animals showed similar growth and maturation,delay in comparison with the CS group. At PND30-35, whilehole pocking number and social exploration index were decreasedin the VS group, exploratory and social behaviours in the VEE groupdid not differ from CS. VPA rats evidenced lower MBP expression,decreased number of CC1+OL and increased PDGFαR+OL but nochanges in tomato lectin or GFAP levels. EM of CC from VPA animalsrevealed lower percentage of myelinated axons and aberrantmyelin; both myelin alterations were ameliorated in VEE animals.Our results indicate that defective OL maturation could contribute tomyelin defects seen in VPA animals. EE can prevent the behaviouralimpairment seen in pre-pubertal stage of VPA animals as well as thestructural myelin alterations observed in the CC of VPA group.