PERSONAL DE APOYO
UDOVIN lucas
artículos
Título:
Consequences of excessive plasticity in the hippocampus induced by perinatal asphyxi
Autor/es:
G.E. SARACENO, L.G. CACERES, L. GUELMAN, R. CASTILLA, L.D. UDOVIN, M.H. ELLISMAN, M.A. BROCCO, F. CAPAN
Revista:
EXPERIMENTAL NEUROLOGY
Editorial:
ACADEMIC PRESS INC ELSEVIER SCIENCE
Referencias:
Lugar: Amsterdam; Año: 2016
ISSN:
0014-4886
Resumen:
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.