Consequences of excessive plasticity in the hippocampus induced by perinatal asphyxi

SARACENO G. E; CACERES L.G; GUELMAN L; CASTILLA R; UDOVIN L.D; ELLISMAN MH; BROCCO, M.A; 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 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.