Altered hippocampal neuronal organization and NCAM expression in an animal model of autism

MG CODAGNONE, MF PODESTÁ, NA UCCELLI, A REINÉS

Buenos Aires

Congreso; 5th ISN Special Conference on “Synapses and dendritic spines in health and disease”, International Society for Neurochemistry (ISN); 2012

Autism is a severe neurodevelopmental disorder with no clear neurobiological basis. In the past few years, research has been focused on synaptic alterations and adhesion molecules have been proposed to have a major role in the etiology. Indeed, autism is considered among the newly described synaptopathies. 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 neural cell adhesion molecule (NCAM) expression pattern as a key determinant of synaptic adhesion. VPA animal´s behavioral testing was performed in two different developmental stages. When tested at early postnatal days, VPA animals showed delayed maturation evidenced not only by growth delay, measured as lower body weight, but also by altered negative geotaxis and delayed eyes opening. Higher latencies to nest seeking response mediated by olfactory system were also seen. Furthermore, when testing swimming performance, delayed motor development and reflexes integration was evidenced. VPA rats were also tested during adolescence and showed decreased exploratory activity and a tendency to 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, increased NCAM immunostaining was found in the CA3 of VPA animals. Maturational delay and abnormal behavior of VPA animals, evidenced by hippocampal dependent tests, correlate with morphological changes and structural disorganization in this area. Additionally, increased NCAM expression suggests 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.