PERSONAL DE APOYO
Consequences of excessive plasticity in the hippocampus induced by perinatal asphyxi
G.E. SARACENO, L.G. CACERES, L. GUELMAN, R. CASTILLA, L.D. UDOVIN, M.H. ELLISMAN, M.A. BROCCO, F. CAPAN
ACADEMIC PRESS INC ELSEVIER SCIENCE
Lugar: Amsterdam; Año: 2016
Perinatal asphyxia (PA) is one of the most frequent risk factors for severalneurodevelopmental disorders (NDDs) of presumed multifactorial etiology. Dysfunction ofneuronal connectivity is thought to play a central role in the pathophysiology of NDDs.Because underlying causes of some NDDs begin before/during birth, we asked whether thisclinical condition might affect accurate establishment of neural circuits in the hippocampusas a consequence of disturbed brain plasticity. We used a murine model that mimics thepathophysiological processes of perinatal asphyxia. Histological analyses of neurons(NeuN), dendrites (MAP-2), neurofilaments (NF-M/Hp) and correlative electronmicroscopy studies of dendritic spines were performed in Stratum radiatum of thehippocampal CA1 area after postnatal ontogenesis. Protein and mRNA analyses wereachieved by Western blot and RT-qPCR. Behavioral tests were also carried out. NeuNabnormal staining and spine density were increased. RT-qPCR assays revealed a β-actinmRNA over-expression, while Western blot analysis showed higher β-actin protein levelsin synaptosomal fractions in experimental group. M6a expression, protein involved infilopodium formation and synaptogenesis, was also increased. Furthermore, we found thatPI3K/Akt/GSK3 pathway signaling, which is involved in synaptogenesis, was activated.Moreover, asphyctic animals showed habituation memory changes in the open field test.Our results suggest that abnormal synaptogenesis induced by PA as a consequence ofexcessive brain plasticity during brain development may contribute to the etiology of theNDDs. Consequences of this altered synaptic maturation can underlie some of the laterbehavioral deficits observed in NDDs.