Against all odds? Neuronal recovery is possible even in conditions of reactive gliosis in a model of sleep apnea by intermittent hypoxia.

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

Charleston, EEUU (2009).

Congreso; Meeting of the American Society for Neurochemistry; 2009

American Society for Neuroscience (ASN),

Sleep apnea (SA) pathology has high prevalence, morbidity and mortality. SA produces repetitive events of breathing cessation during sleep inducing intermittent hypoxia (IH). Exposure of experimental animals to IH reproduces the pathological effects of SA in the brain. Using a model of SA by exposure to IH, we analyzed the neuronal and glial status after 1, 3, 5, and 10 days of IH exposure (IH1; IH3; IH5; IH10). Rats were subjected to IH alternating the hypoxic condition (90% N2, 10% O2) with normoxia (21% O2, 79% N2) (cycles of 6 min / 8h per day). Brains were analyzed by immunocytochemistry and morphometry. The hippocampal and cortical astrocytes responded to the IH with hypertrophy and hyperplasia beginning at IH1 and reaching a peak in IH10. The expression of S100B, glial factor involved in neuronal survival, increased with peaks at IH3 and IH10. HIF-1á, transcription factor associated with hypoxia, and MDR1 (a gene controlled by HIF-1á) had an early increase demonstrating the induction of this cascade of classical hypoxia. While in IH3 we demonstrated neuronal death and gross morphological alterations in the dendritic trees, by IH-10 we could not demonstrate neuronal death or nuclear alterations. Surprisingly, a phenomenon of sprouting was present in these animals by IH10. Our results showed that IH induces neuronal and glial alterations in two brain areas closely related to cognitive disorders seen in patients with SA. Interestingly, neuronal alterations are larger at shorter exposure times while a recovery was found later coexisting with reactive gliosis usually associated with detrimental conditions for neuronal survival. Supported by CONICET, ANPCYT, IBRO.