Astrocytes as guardians in the Central Nervous System: Early glial response to neuronal degeneration induced by sleep apnea

ROLANDO X. AVILES REYES, MARIA FLORENCIA ANGELO, ALEJANDRO VILLARREAL , ALBERTO JAVIER RAMOS

Washington, EEUU

Congreso; Society for Neuroscience; 2008

Society for Neuroscience

Astrocytes as guardians in the Central Nervous System:  Early glial response to neuronal degeneration induced by sleep apnea   Rolando X. Aviles Reyes, Maria Florencia Angelo, Alejandro Villarreal , Alberto Javier Ramos   Laboratorio de Neuropatología Molecular, Instituto de Biología Celular y Neurociencia “Prof. E. De Robertis”, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155 3er piso (1121) Ciudad de Buenos Aires, Argentina.     Sleep apnea (SA) is a largely common pathology state that produces intermittent hypoxia (IH) to the brain and serious cognitive deficits. There are few evidences of the early glial and neuronal response to SA. In an experimental model of SA we studied the cellular alterations induced by 1 or 3 days exposure to cycles of normobaric hypoxia (6 min each, 10% O2, 8 h per day). Adult male Wistar rats (250-300g) were exposed to IH and brains were processed for immunocytochemistry and image analysis. Our results showed increased number and significant hypertrophy in GFAP-stained astroglial cells from corpus callosum, parietal brain cortex and hippocampus starting in IH1 group. Early signs of neuronal degeneration including cytoplasmic localization of neuronal nuclear marker NeuN and shorter MAP-2 positive dendrites were detected later in the IH3 group. Evidences of apoptotic cell death detected by Nissl staining and by nuclear morphology were observed in hippocampal CA1 pyramidal neurons and cortical layers IV-V in IH3 group. Upregulation of hypoxia induced factor (HIF-1a) was observed in cortex and hippocampal areas with a maximal peak in IH1 group. Increased expression of MDR-1 (a HIF-1a driven gene) was observed in IH3. These results show that even a short number of cycles of hypoxia are enough to induce reactive gliosis evidenced before signs of neuronal degeneration are detectable in critical areas involved in cognitive processes such as brain cortex and hippocampus. The results obtained reinforce the idea that astrocytes immediately respond to alterations in neuronal microenvironment acting as sensors of neuronal stress.        Keywords: sleep apnea, hypoxia, glia, reactive gliosis, HIF, RAGE, S100B