IBCN   20355
INSTITUTO DE BIOLOGIA CELULAR Y NEUROCIENCIA "PROFESOR EDUARDO DE ROBERTIS"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
RAGE and NF-kB are involved in neuronal death and reactive gliosis induced by Intermittent Hypoxia.
Autor/es:
ANGELO MF; AGUIRRE AI; LUKIN J; VILLARREAL A; EPSTEIN A; JERUSALINSKY DA; ALBERTO JAVIER RAMOS
Lugar:
Ciudad Autonoma de Buenos Aires
Reunión:
Simposio; II Simposio Franco-Argentino de Neurociencias.; 2012
Institución organizadora:
LIA DEVENIR: Laboratorio Internacional Asociado para el Desarrollo de Vectores Neurotropicos para la Investigacion en Neurociencias - (CNRS / Univ. Lyon1 y CONICET / UBA)
Resumen:
RAGE and NF-kB are involved in neuronal death and reactive gliosis induced by Intermittent Hypoxia Angelo MF, Aguirre AI, Lukin J, Villarreal A, Epstein A, Jerusalinsky DA, Ramos AJ Sleep apnea (SA) produces important alterations in learning, memory and cognitive performance due to the cyclic episodes of intermittent hypoxia (IH). Using an experimental model of SA by IH, we have previously demonstrated early reactive gliosis and neuronal alterations that ranged from decreased dendrite length and abnormal nuclear morphology to neuronal death in hippocampus and brain cortex, two anatomical areas that are related to the cognitive impairments observed in SA patients (Aviles-Reyes et al., 2010). We also demonstrated that IH induces the over-expression of the Receptor for Advanced Glycation End Products (RAGE) and its ligand S100B as well as the activation of the downstream NF-kB signaling. In this work we analyzed the contribution of the S100B-RAGE-NFkB pathway to the IH-induced glial and neuronal alterations by gain- and loss- of function approaches. Primary mixed cultures (glia and neurons) exposed to IH showed neurite retraction and astrocytic stellation that were prevented by anti-RAGE neutralizing antibodies or by the over-expression of a DN-RAGE delivered by HSV-derived amplicon. In vivo, RAGE blockage decreased neuronal alterations and reactive gliosis in IH exposed animals while S100B blockage did not reverse neuronal alterations but reduced reactive gliosis. Chemical blockage of downstream effector NF-κB also reduced neuronal alterations in IH animals but showed detrimental effects in normoxic conditions. In naïve animals, overexpression of the amplicon-delivered FL-RAGE, but not DN-RAGE, resulted in alterations of neuronal morphology similar to those observed in hypoxic animals. Taken together, these results indicate that overactivation of the S100B-RAGE-NFκB pathway is probably involved in the neuronal alterations and reactive gliosis observed in IH-exposed animals.