Early neuronal and glial alterations in an experimental model of sleep apnea by intermittent hypoxia

AVILES REYES RX, ANGELO MF, VILLARREAL A, LAZAROWSKI A, RAMOS AJ

NEUROBIOLOGY OF DISEASE

Enviado a publicacion YNBD-S-08-00187

Año: 2008

0969-9961

Obstructive sleep apnea (SA) is a largely common pathological state that produces intermittent hypoxia (IH) to the brain and serious cognitive deficits. There are few evidences of the early brain response to SA at the cellular level. In an experimental model of SA we studied the early glial and neuronal alterations induced by 40 or 110 cycles of normobaric hypoxia (6 min each, 10% O2, 8 h per day) equivalent to 1 and 3.5 days of IH. Increased number and significant hypertrophy were observed in astroglial cells from corpus callosum, parietal brain cortex and hippocampus. Cytoplasmic localization of neuronal nuclear marker NeuN as well as alterations in MAP-2 distribution were observed in the hippocampal pyramidal neurons of the CA1 area and in cortical layers IV-V. Upregulation of HIF-1a and the HIF-1a driven gene mdr-1 was also observed in cortex and hippocampal areas. Increased expression of the proinflammatory receptor RAGE and its binding partner S100B were also observed. These results show that a short number of cycles of hypoxia are enough to induce reactive gliosis, inflammation and severe alterations in neurons in critical areas involved in cognitive processes such as brain cortex and hippocampus. These areas are involved in the memory dysfunctions and other cognitive disorders observed in SA human patients.