Corpus callosum connectivity alterations in the valproic acid experimental model of autism

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

Buenos Aires

Congreso; 2nd FALAN congress; 2016

Federación Latinoamericana y del Caribe de sociedades de neurociencia

Autism Spectrum Disorders (ASD) are a group of neurodevelopmental disabilities with unknown biological basis. A long-distance hypoconnectivity and short-distance hyperconnectivity hypothesis has emerged for these disorders. Structural and functional alterations in the corpus callosum (CC),the main structure that contains axonal tracts connecting brain hemispheres, have been reported in ASD patients. Changes in adhesion molecule expression, neuroinflamation and white matter alterations have been described in different brain areas both in AS& patients and animal models.The aim of this work was to elucidate cellular and molecular alterations in CC sub-regions from rats prenatally exposed to valproic acid (VPA). For this purpose, at postnatal day 35, we studied cellular organization by DAPI staining in CC rostral body and posterior midbody. Also, we evaluated the expression of the neural cell adhesionmolecule NCAM and its polysialilated form PSA-NCAM and studied glial cells by tomato lectin (microglia), glial fibrillary acidic protein (GFAP, atrocytes), CC1 (oligodendrocytes) and myelin basic protein (MBP) by immunohistochemistry. In VPA rats, we found decreased NCAM expression levels in rostral CC but not in the posterior region, accompanied by a robust diminution in PSA-NCAM levels in both CC sub-regions. We also observed cellular disorganization in the CC fromVPA animals but no changes were found in microglia or astroglia. CC1 and MBP immunoreactivity decreased in both CC sub-regions of VPA rats. In summary, our results indicate long-distance connectivity defects as well as a spread reduction in mature oligodendrocytes and myelin content in the absence of microgliosis and astrogliosis in both CC sub-regions studied in VPA rats.