IBCN   20355
INSTITUTO DE BIOLOGIA CELULAR Y NEUROCIENCIA "PROFESOR EDUARDO DE ROBERTIS"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
RAGE and NF-kB activation cause neuronal death in a model of Sleep Apnea by Intermittent Hypoxia.
Autor/es:
ANGELO MF; AVILES REYES RX; VILLARREAL A; LUKIN J; RAMOS AJ
Lugar:
Florencia
Reunión:
Congreso; 8th IBRO World Congress of Neuroscience; 2011
Resumen:
Sleep apnea (SA) produces important alterations in learning, memory and cognitive performance. Using an experimental model of SA by intermittent hypoxia (IH), we previously demonstrated early reactive gliosis and neuronal alterations that ranged from decreased dendrite length to neuronal death in hippocampus and brain cortex, two anatomical areas related to cognitive impairments observed in patients (Aviles-Reyes et al., 2010). We also demonstrated 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. Since S100B-RAGE-NF-kB could activate genes related to cell survival or death, we performed loss of function studies using neutralizing antibodies anti-RAGE, anti-S100B or NF-kB chemical blockage in animals exposed to IH. After intrahippocampal administration of these blockers, the animals were exposed to IH (6min 10% O2 - 6 min 21% O2, 8hs/day, 3 days). Neuronal nuclei morphology and reactive gliosis were studied in the hippocampal CA1 area. RAGE blockage decreased neuronal alterations and reactive gliosis in IH animals but induced both features in normoxic conditions. Surprisingly, anti-S100B blocking antibodies did not reverse IH-induced neuronal alterations but indeed reduced reactive gliosis. NF-kB blockage by sulfasalazine diminished neuronal alterations in IH animals but showed detrimental effect in normoxic conditions. Taken together, these results indicate that S100B-RAGE-NF-kB pathway could participate in the developmet of neuronal alterations and reactive gliosis observed in the model of sleep apnea by intermittent hypoxia.