Assesing the neuronal role in hippocampal hypoconnectivity in the VPA model of autism

TRAETTA MARIANELA; CODAGNONE MARTIN; UCCELLI NONTHUE; MALLEVILLE CORPA MARÍA JOSÉ; ZÁRATE SANDRA; REINÉS ANALÍA

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

Autism spectrum disorders are characterized by impairments in social interaction and repetitive-stereotyped behaviours. Applying the VPA model, we reported in the hippocampus of juvenile VPA rats: a decrease in synaptophysin (SYN) along with an increased expression of the neural cell adhesion molecule (NCAM) and a decrease in its polysialylated form (PSA-NCAM). The aim of this study was to evaluate synapse formation and remodeling of primary hippocampal neurons from VPA or control male pups. Cytoskeletal and synaptic markers were evaluated by immunocytochemistry and WB. Neurons from VPA animals displayed a reduced dendritic tree (reduced MAP2 area), a reduced number of glutamatergic synapses (decreased vGLUT and PSD-95 puncta number) and NMDA receptor clusters (decreased NR1 puncta number and individual puncta area). These neurons exhibited reduced number of functional synapses (FM4-64 labelling) which contained smaller vesicular pools; total NCAM expression increased while PSA-NCAM decreased. While in neurons from control animals glutamate (5μM-3min) induced an NMDA-dependent dendritic retraction and SYN puncta number reduction, neurons from VPA animals were only capable of dendritic retraction without any change in synapse number. Our results indicate that neurons from VPA animals form fewer glutamatergic synapses that exhibit a more adhesive and resistant profile to synaptic remodeling what would contribute to hippocampal hypoconnectivity and reduced synaptic plasticity