Early neuronal alterations in an experimental model of sleep apnea: The S100B-RAGE link

ANGELO F; AVILES R; VILLARREAL A; RAMOS AJ

Buzios, Rio de Janeiro, Brasil

Congreso; I Congreso IBRO/LARC de Neurociencias de América latina, Caribe y Península Ibérica. 1-4 de Septiembre de 2008; 2008

Colegio Colombiano de Neurociencias, Programa de Investigación en Neurociencia (Costa Rica), Sociedad Cubana de Neurociencias, Sociedad Española de Neurociencia, SOCIEDAD MEXICANA DE NEUROCIENCIAS Y NEUROBIOLOGIA, etc

Obstructive sleep apnea (OSA) is a very common silent chronic pathology characterized by intermittent hypoxia (IH). Patients usually reach health care with large complications and cognitive impairment. Receptor for Advanced Glycated End Products (RAGE) is expressed by neurons in hypoxic stress and binds glial factor S100B, increased by IH, to induce apoptosis or survival depending on the concentration. Objectives: Study early neuronal alterations induced by IH and expression of RAGE and S100B. Methods: Adult male Wistar rats were exposed during the sleep phase (8hs/day) to cycles of 6 min of hypoxia (10% O2) and 6 min of normoxia for 40 (1 day, IH40) or 110 cycles (3 days, IH110). Brain sections were processed for immunohistochemistry with antibodies anti microtubule associated protein 2 (MAP2), Neurofilament-200KDa (Nf-200), neuronal nuclear protein NeuN, RAGE, S100B. Sections were also subjected to Toluidine blue (TB), Hoechst staining (HS) and a commercial kit to recognize Active Caspases (Caspatag). Results: IH reduced number of normal NeuN staining in cortex (Cx) layers IV-V from 93.6±5.6% to 87±18.1% (IH40) and 51.4±22.5% (IH110). CA-1 reduction was from 94.7±5.3% to 56.7±27.3% (IH40) and 38±14.8% (IH110). Neurons with normal morphology by TB were also reduced in CA-1 from 94.9±4.1% to 77.9±8.5% (IH110) and CA2/3 from 96.7±2.3% to 75.1±6.1% (IH110). Neuronal death was confirmed by Caspatag and HS that showed apoptotic characteristics in CA-1 and Cx. MAP-2 staining showed CA-1 neurons 33.3±17.5% shorter in IH110. Nf-200 staining showed shorter filaments without statistical significance. RAGE expression was induced by IH in isolated Hippocampus (Hip) and Cx neurons surrounded by astrocytes with increased S100B expression. These RAGE+ neurons did not show degeneration signs. Conclusions: IH induces early severe alterations in Hip and brain Cx neurons going from neurite length alterations to apoptosis. Since RAGE is expressed in neurons from these areas and S100B is available, they might be involved in the determination of neuronal death or survival after IH.