INBIOMED   24026
INSTITUTO DE INVESTIGACIONES BIOMEDICAS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Dissecting the differentiation profile of hippocampal neurons in the VPA rat model of autism: an in vitro approach
Autor/es:
TRAETTA MARIANELA; ZÁRATE SANDRA; UCCELLI NONTHUE; CODAGNONE MARTIN; REINÉS ANALÍA
Lugar:
Mar del Plata
Reunión:
Congreso; LXI Reunión de la Sociedad Argentina de Investigación Clínica; 2016
Resumen:
Autism spectrum disorders (ASD) are a group of neurodevelopmental disabilities characterized by impairments in social interaction and stereotyped behaviors. Prenatal exposure to valproic acid (VPA), a well validated ASD animal model, mimics the main behavioral and neuroanatomical alterations found in these disorders. Regarding the cellular and molecular changes seen in the hippocampus of VPA rats, we previously reported a decrease in synaptic protein synaptophysin (SYN) and the polysialylated form of the neural cell adhesion molecule (PSA-NCAM). We hypothesized that prenatal VPA exposure may modify neuronal differentiation and/or synaptic formation and maturation either directly by epigenetic changes or indirectly through mechanisms involving other cells. Therefore, we tested whether in vitro postnatal hippocampal neurons from VPA rats show similar synaptic and PSA-NCAM expression patterns as those observed in vivo. An in vitro approach was performed by culturing hippocampal neurons from P1-P2 rat pups after in utero (E 10.5) VPA (500 mg/kg) or saline exposure. In order to study neuronal differentiation and synaptic formation, a time course was performed by fixing neurons at different days in vitro (DIV). During early neuronal differentiation in vitro (DIV 3-5), SYN immunostaining was increased in the VPA group. Notably, neurons from this group showed increased actin immunostaining accompanied with abundant dendritic and axonal filopodia. Not all synaptic proteins were increased since PSD-95 levels were lower than in control neurons. Later in culture (DIV 14), in the VPA group, a reduction was found both in SYN puncta area and number as well as a decrease in PSA-NCAM immunoreactivity. To sum up, we observed transient changes in hippocampal postnatal neurons from VPA animals which correlate with in vivo founding. Our results suggest that the early increase in SYN expression and actin sprouting might well represent a mechanism to promote synapse formation.