title: Consequences of excessive plasticity in the hippocampus induced by perinatal asphyxia.
abstract: 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 the pathophysiology of NDDs. Because underlying causes of some NDDs begin before/during birth, we asked whether this clinical condition might affect accurate establishment of neural circuits in the hippocampus as a consequence of disturbed brain plasticity. We used a murine model that mimics the pathophysiological processes of perinatal asphyxia. Histological analyses of neurons (NeuN), dendrites (MAP-2), neurofilaments (NF-M/Hp) and correlative electron microscopy studies of dendritic spines were performed in Stratum radiatum of the hippocampal CA1 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 assays revealed a β-actin mRNA over-expression, while Western blot analysis showed higher β-actin protein levels in synaptosomal fractions in experimental group. M6a expression, protein involved in filopodium formation and synaptogenesis, was also increased. Furthermore, we found that PI3K/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 of excessive brain plasticity during brain development may contribute to the etiology of the NDDs. Consequences of this altered synaptic maturation can underlie some of the later behavioral deficits observed in NDDs.
authors: ININCA, Universidad de Buenos Aires (UBA)-CONICET, Buenos Aires, Argentina.
authors: G E
authors: GE
authors: Saraceno
authors: Facultad de Medicina (UBA) CEFyBO-CONICET, Buenos Aires, Argentina.
authors: L G
authors: LG
authors: Caceres
authors: Facultad de Medicina (UBA) CEFyBO-CONICET, Buenos Aires, Argentina.
authors: L R
authors: LR
authors: Guelman
authors: ININCA, Universidad de Buenos Aires (UBA)-CONICET, Buenos Aires, Argentina.
authors: R
authors: R
authors: Castilla
authors: ININCA, Universidad de Buenos Aires (UBA)-CONICET, Buenos Aires, Argentina.
authors: L D
authors: LD
authors: Udovin
authors: Department of Neuroscience, Department of Neuroscience, National Center for Electron Microscopy and Imaging Research, UCSD, United States.
authors: M H
authors: MH
authors: Ellisman
authors: Instituto de Investigaciones Biotecnológicas-Instituto Tecnológico de Chascomús (IIB-INTECH), UNSAM-CONICET, Buenos Aires, Argentina.
authors: M A
authors: MA
authors: Brocco
authors: ININCA, Universidad de Buenos Aires (UBA)-CONICET, Buenos Aires, Argentina; Instituto de Ciencias Biomédicas, Facultad de Ciencias de la Salud, Universidad Autónoma de Chile, Chile. Electronic address: fcapani@fmed.uba.ar.
authors: F
authors: F
authors: Capani
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001237:Asphyxia / Q000473:pathology* / Q000503:physiopathology; D001362:Avoidance Learning / Q000502:physiology; D049229:Dendritic Spines / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D005106:Exploratory Behavior / Q000502:physiology; D005260:Female; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology* / Q000648:ultrastructure; D008854:Microscopy, Electron; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009473:Neuronal Plasticity / Q000502:physiology*; D011247:Pregnancy; D017966:Pyramidal Cells / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology; D013347:Subcellular Fractions / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D009419:Nerve Tissue Proteins; D012333:RNA, Messenger
keywords: Habituation memory; M6a; Neurodevelopmental disorders; PI3K/Akt/GSK3 pathway; Synaptogenesis; β-Actin