INVESTIGADORES
BROCCO Marcela Adriana
congresos y reuniones científicas
Título:
Hippocampal synaptogenesis and dendritic spine density enhancement after perinataLasphyxia
Autor/es:
SARACENO EZEQUIEL; GALEANO PABLO; CÁCERES LG; ROMERO JUAN I; HOLUBIEC MARIANA; LÓGICA T; MUÑIZ JA; GUELMAN L; CASTILLA R; BROCCO MARCELA ADRIANA; CAPANI FRANCISCO
Reunión:
Congreso; ll° COLLOQUE Sociétés des Neurosciences; 2013
Resumen:
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 β-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.