Hippocampal synaptogenesis and dendritic spine density enhancement after perinatal asphyxia

SARACENO, EZEQUIEL; GALEANO, PABLO; CÁCERES, LUCILA; ROMERO, JUAN IGNACIO; HOLUBIEC, MARIANA; LOGICA, TAMARA; MUÑIZ, JAVIER; GUELMAN, LAURA; CASTILLA, ROCÍO; BROCCO, MARCELA; CAPANI, FRANCISCO

Lyon

Congreso; XI Colloque du Société des Neurosciences; 2013

Société des Neurosciences

Even though the underlying causes of neurodevelopmental disorders (NDDs) are known to onset before birth, symptoms may not appear until months or years later. It is thought that dysfunction of neuronal connectivity could play a central role in the pathophysiology of NDDs. Perinatal asphyxia (PA) is an important risk factor for several NDDs of presumed multifactorial etiology since it affects the accurate establishment of neural circuits during a period of apparent normal development. The lack of knowledge of the underlying mechanisms of this dysfunction, prompted us to investigate the morphological changes in the neuronal cytoskeleton induced by PA in a murine model. Consequences of PA on neuronal and glial CA1 hippocampal components, which are involved in the establishment of neuronal circuits, were analyzed at 30 days of age. Results indicated that asphyctic rats showed an increment of NeuN abnormal staining in stratum radiatum of the hippocampal CA1 area. No changes were observed in GFAP+ astrocytes morphology, neither in MAP2+ dendrites morphology, nor in the phosphorylation status of medium and heavy neurofilaments (NF H/Mp). Regarding the consequences of PA on dendritic spines, an increase in mushroom-type protrusion was observed using confocal and electron microscopy. Real-time PCR assays revealed an over-expression of beta-actin mRNA, while Western blot analysis showed higher β-actin protein levels in synaptosome fractions of asphyctic animals. In addition, these alterations were accompanied by an increase in the expression of M6a, a protein involved in spinogenesis and synaptogenesis. When we analyzed the possible signaling pathways involved in synaptogenesis induced by PA, PI3K/Akt/GSK3 pathway was activated. Surprisingly, asphyctic animals showed better cognitive performance than control rats. Taken together, these results strongly support the hypothesis that abnormal synaptogenesis during brain development induced by PA may contribute to the etiology of the NDDs.