Synaptic and glial modifications induced by perinatal asphyxia

F. CAPANI, M. HERRERA, A. GONZALEZ, C. QUARRACINO, S. MUCCI, R. KOLLIKERS-FRERS

Congreso; Society of Neurocience meetig; 2016

Perinatal asphyxia (PA) induces short and long term synaptic and cytoskeleton alterations that have been associated with neuronal cell death following hypoxia. The aim of this study was to elucidate the mechanisms underlying this dysfunction. We used a well-established murine model of PA, which was modified in our laboratory. After one and 2 months of the PA insult, an increase in the F-actin staining in neostriatum and hippocampus synapses was observed using correlative fluorescent electron microscopy for phalloidin-eosin. Mushroom-shaped spines showed the most consistent staining. Strong alterations in the dendrite and astroglial cytoskeleton organization were found at 4 months of PA. After 6 months of PA, we observed an increase in ubiquitination level and an increment of rat neostriatum post synaptic densities (PSDs) thickness, which was related to the duration and severity of the hypoxic insult. Using 3-d reconstruction and electron tomography we observed clear signs of damage in the asphyctic PSDs. These changes were correlated with intense staining for ubiquitin. Finally, in 18 months old rat we encountered a reduction in the number of synapses in the PA animals related with a decrease in BDNF staining. Overall, these results demonstrate that synaptic dysfunction following PA might be produced by early changes in the actin organization and long-term misfolding and aggregation of proteins in the PSDs.