Inter-hemispheric hypo-connectivity and regional metabolic hyper-activity in an experimental model of autism.

LEVANOVICH N; URRUTIA L; VAZQUEZ S; CODAGNONE MG; TRAETTA ME; PASQUINI J; UCCELLI NA; ROSATO SIRI MV; FALASCO G; REINÉS A

Córdoba

Congreso; XXXIII Reunión Anual de la Sociedad Argentina de Investigación en Neurociencias; 2018

Sociedad Argentina de Investigación en Neurociencias (SAN)

Autism spectrum disorders (ASD) are a group of neurodevelopmental disabilities characterized by alterations in brainconnectivity and neuroinflammation. In accordance with thelong-distance hypo-connectivity and local hyper-connectivityhypothesis, previous studies in our laboratory with the valproic acid (VPA) model demonstrate connectivity alterationsand reactive gliosis in the prefrontal cortex and hippocampus of VPA rats. The aim of this work was to evaluate thebrain metabolic activity and the structure of the corpus callosum (CC) in VPA animals. For this purpose, glial cells in theCC were studied at PND 36 by CC1, PDGFaR, GFAP andtomato lectin staining. Also, CC ultrastructure was assessedby electron microscopy (EM). Evaluated by positron emission tomography, glucose uptake was increased in local areasalong the brain of VPA rats, while it was decreased whenconsidered the whole forebrain. In the CC of VPA rats, thenumber of CC1þ cells diminished and number of PDGFþcells increased, in the absence of astrogliosis or microgliosis.Concomitantly, EM showed less myelinated axons and aberrant myelin in the CC of VPA rats. To sum up, VPA animalsexhibit hyper-metabolism in circumscribed brain areas alongwith global hypo-metabolism. Concurrently, CC myelinationin VPA animals is disrupted, accompanied by an altered balance in the oligodendroglia lineage. Taking together, ourfindings support the local hyper-activity and long-distancehypo-connectivity hypothesis in ASD.