Hippocampal synaptic alterations in an animal model of autism.

CODAGNONE M; PODESTÁ MF; UCCELLI NA; TRAETTA ME; REINÉS A

Long Beach

Congreso; 45th Annual ASN Meeting; 2014

American Society for Neurochemistry

Autism is a severe neurodevelopmental disorder with an early onset and no clear neurobiological basis. It is considered among the newly described synaptopathies and adhesion molecules have been proposed to have a major role in the etiology. The animal model of autism induced by rat prenatal exposure to Valproic Acid (VPA) evidenced behavioral and neuroanatomical alterations similar to those seen in autistic patients. The aim of this work was to study in VPA animals the hippocampal cytoarchitecture and the expression pattern of structural (SYN, synaptophysin) and glial (GFAP, glial fibrillary acid protein) markers and of key determinants of synaptic adhesion (neural cell adhesion molecule, NCAM, and its polysialylated variant PSA-NCAM). VPA animal´s behavioral testing was performed in two different developmental stages. At early postnatal days, VPA animals showed delayed maturation evidenced not only by lower body weight, but also by altered negative geotaxis and delayed eyes opening. Higher latencies to nest seeking response and a deficit in swimming performance were evidenced. VPA rats were also tested during adolescence and showed decreased exploratory activity and lower interaction between partners when evaluating social play behavior. At this stage (at postnatal day 35), Nissl staining showed alterations in CA3 hippocampal cytoarchitecture. Neuronal participation in this structural disorganization was confirmed by immunofluorescence with the neuronal marker NeuN. Moreover, decreased SYN and increased NCAM and GFAP immunostaining was found in the CA3 of VPA animals. Decreased PSA-NCAM immunostaining was seen in CA3 and dentated gyrus. Maturational delay and abnormal behavior of VPA animals, evidenced by hippocampal dependent tests, correlate with morphological changes and structural disorganization in this area. Additionally, the deficit in synaptic markers and the imbalance of NCAM/PSA-NCAM expression suggest a different synaptic adhesion profile in the hippocampus. In sum, a complex neuronal organization and alterations in connectivity could lead the way to unravel the neural basis of autism.