RAGE and NF-κB are involved in neuronal death and reactive gliosis induced by Sleep Apnea.

ANGELO MF; AVILES REYES RX; VILLARREAL A; LUKIN J; ALBERTO JAVIER RAMOS

Huerta Grande, Córdoba

Congreso; XXVI Congreso Anual SAN (Sociedad Argentina de investigación en Neurociencias); 2011

Sociedad Argentina de investigación en Neurociencias

"RAGE and NFkB are involved in neuronal death and reactive gliosis induced by Sleep Apnea" María Florencia Angelo, Rolando X Aviles Reyes, Alejandro Villarreal, Jerónimo Lukin, Alberto Javier Ramos Instituto de Biologia Celular y Neurociencia Prof. E. De Robertis jramos@fmed.uba.ar Sleep apnea (SA) produces cognitive alterations. In an experimental model of SA by intermittent hypoxia (IH) we previously showed reactive gliosis, neuronal degeneration, overexpression of the Receptor for Advanced Glycation End Products (RAGE) and its ligand S100B. Since S100B/RAGE/NFkB pathway can promote either cell survival or death; we studied NFkB activity using reporter mice and performed loss of function assays in vivo and in vitro in neuro-glial culture. NFkB activity was increased after IH. Intrahippocampal injections of RAGE neutralizing antibodies decreased neuronal alterations and reactive gliosis in IH animals but were detrimental in normoxia. Endogenous S100B blockage did not reverse neurodegeneration but reduced reactive gliosis after IH. NFkB blockage with SFZ (NFkB inhibitor) improved neuronal survival after IH but was detrimental in normoxic conditions. Since oxidative stress is recognized as the main detrimental effect of SA, primary neuro-glial mixed cultures (astrocytes and neurons) were exposed to 150 uM H2O2 for 30 min and showed changes in astroglial morphology that were reversed by RAGE blockage. Taken together, these results indicate that over-activity of the S100B/RAGE/NFkB pathway could promote reactive gliosis and neuronal degeneration after IH.