Consequences of excessive plasticity in the hippocampus induced by perinatal asphyxia.

SARACENO GE, CACERES LG, GUELMAN LR, CASTILLA R, UDOVIN LD, ELLISMAN MH, BROCCO MA, CAPANI F

EXPERIMENTAL NEUROLOGY

ACADEMIC PRESS INC ELSEVIER SCIENCE

Lugar: Amsterdam; Año: 2016

0014-4886

Perinatal asphyxia (PA) is one of the most frequent risk factors for several neurodevelopmental disorders (NDDs)of presumed multifactorial etiology. Dysfunction of neuronal connectivity is thought to play a central role in thepathophysiology of NDDs. Because underlying causes of some NDDs begin before/during birth, we asked whetherthis clinical condition might affect accurate establishment of neural circuits in the hippocampus as a consequenceof disturbed brain plasticity. We used a murine model that mimics the pathophysiological processes of perinatalasphyxia. Histological analyses of neurons (NeuN), dendrites (MAP-2), neurofilaments (NF-M/Hp) and correlativeelectron microscopy studies of dendritic spines were performed in Stratum radiatum of the hippocampalCA1 area after postnatal ontogenesis. Protein and mRNA analyses were achieved by Western blot and RT-qPCR.Behavioral tests were also carried out. NeuN abnormal staining and spine density were increased. RT-qPCR assaysrevealed a β-actin mRNA over-expression, while Western blot analysis showed higher β-actin protein levels insynaptosomal fractions in experimental group. M6a expression, protein involved in filopodium formation andsynaptogenesis, was also increased. Furthermore, we found that PI3K/Akt/GSK3 pathway signaling, which is involvedin synaptogenesis, was activated. Moreover, asphyctic animals showed habituation memory changes inthe open field test. Our results suggest that abnormal synaptogenesis induced by PA as a consequence of excessivebrain plasticity during brain development may contribute to the etiology of the NDDs. Consequences of thisaltered synaptic maturation can underlie some of the later behavioral deficits observed in NDDs.