INVESTIGADORES
ZARATE Sandra Cristina
congresos y reuniones científicas
Título:
Evidences of hypoconnectivity in the valproic acid rat model of autism spectrum disorder
Autor/es:
UCCELLI NONTHUE; TRAETTA MARIANELA; CODAGNONE MARTIN; ROSATO SIRI MARÍA VICTORIA; ZÁRATE SANDRA; PASQUINI JUANA; REINÉS ANALÍA
Reunión:
Congreso; 26th ISN-ESN Biennial Meeting; 2017
Resumen:
Autism spectrum disorders (ASD) are classified as synaptopathies and characterized by impairment in social interaction, verbal and nonverbal communication and repetitive and stereotyped behaviors. Hypoconnectivity has been suggested in ASD patients, particularly in the corpus callosum (CC). In the valproic acid (VPA) animal model of ASD, we have previously postulated local hipocamppal hypoconnectivity based on the decrease in synaptic protein synaptophysin (SYN) seen in these animals. The aim of this work was to characterize the CC structure of VPA animals and evaluate neuronal differentiation and synaptic formation of hippocampal neurons from VPA animals. Valproic acid (500 mg/kg) or saline were prenatally administered on embryonic day 10.5 (control and VPA animals, respectively). Hippocampal neurons were cultured from PND1-2 pups. At DIV3-5, hippocampal neurons from VPA animals exhibited increased complexity in dendritic and filopodia development along with increased SYN immunostaining. As differentiation proceeded (DIV 14), SYN puncta area and number as well as PSA-NCAM immunoreactivity in the VPA group were lower than in controls. Labeling of presynaptic boutons with FM4-64 dye revealed a diminution of functional synapses in the VPA group at this stage. The anterior region of CC from VPA animals showed a disorganized cellular arrangement in the absence of changes in GFAP (astrocytes) or Iba-1 (microglia) immunostainings. Immunoreativities for CC1 (matureoligodendrocytes) and myelin basic protein (MBP) were reduced. Myelin of axonal tracts from VPA animals exhibited an unorganized disposition. Our results suggest that neuronal changes and myelin defects in the hippocampus and CC of VPA animals, respectively, could underlie alteredconnectivity postulated for these brain areas in ASD.