Evidences of hypoconnectivity in the valproic acid rat model of autism spectrum disorder.

REINÉS A; CODAGNONE M; PASQUINI J; TRAETTA ME; ZÁRATE S; UCCELLI NA; ROSATO SIRI V

París

Congreso; Congreso de la International Society for Neurochemistry; 2017

International Society for Neurochemistry

Autism spectrum disorders (ASD) are classified as synaptopathiesand characterized by impairment in social interaction,verbal and nonverbal communication and repetitive and stereotypedbehaviors. Hypoconnectivity has been suggested in ASD patients,particularly in the corpus callosum (CC). In the valproic acid (VPA)animal model of ASD, we have previously postulated localhipocamppal hypoconnectivity based on the decrease in synapticprotein synaptophysin (SYN) seen in these animals. The aim of thiswork was to characterize the CC structure of VPA animals andevaluate neuronal differentiation and synaptic formation of hippocampalneurons from VPA animals. Valproic acid (500 mg/kg) orsaline were prenatally administered on E 10.5 (control and VPAanimals, respectively). At DIV 3?5, primary hippocampal neuronsfrom VPA animals exhibited increased complexity in dendritic andfilopodia development along with increased SYN immunostaining.As differentiation proceeded (DIV 14), SYN puncta area andnumber as well as PSA-NCAM immunoreactivity in the VPA groupwere lower than in controls. Labeling of presynaptic boutons withFM4-64 dye revealed a diminution of functional synapses in theVPA group at this stage. The anterior region of CC from VPAanimals showed a disorganized cellular arrangement in the absenceof changes in GFAP (astrocytes) or Iba-1 (microglia) immunostainings.Immunoreativities for CC1 (mature oligodendrocytes) andmyelin basic protein were reduced. Myelin of axonal tracts fromVPA animals exhibited an unorganized disposition. Our resultssuggest that neuronal changes and myelin defects in the hippocampus and CC of VPA animals, respectively, could underliealtered connectivity postulated for these brain areas in ASD.