NF-kB inhibition affects survival of cortical neurons in a model of sleep apnea by intermittent hypoxia.

ANGELO MF, AVILÉS-REYES RX, VILLARREAL A, RAMOS AJ.

Huerta Grande – Córdoba Argentina

Congreso; I Reunión Conjunta de Neurociencias; 2009

Sociedad Argentina de Investigacion en Neurociencias-Taller de Neurociencias

Sleep apnea (SA) is a human pathology that produces important alterations in the cognitive performance. Using an experimental model of SA by intermittent hypoxia (IH), we previously demonstrated early severe alterations and neuronal death in hippocampus and brain cortex. However, neuronal loss was limited. To analyze the NFKB role in the neuronal survival in IH conditions, we blocked NFKB activation in IH animals by daily intracerebral infusions of sulphazalazine (SFZ). Three days after the surgery to fix the needle, male Wistar rats were infused with XXXX sulphazalazine and exposed to IH cycles (alternating 10% - 21% O2) every 6 min during 8h/day (sleep phase) for 3 days. Then, rats were anaesthetized and fixed by perfusion. Immunohistochemistry with neuronal specific nuclear marker (NeuN) and dendritic marker MAP-2 was performed to evaluate the integrity of the neuronal cells. Nuclear p65 NFKB abundance was used to verify the effectiveness of SFZ infusion and to determine the area were NFKB activation was blocked. SFZ infusion induced a persistence of cytoplasmic p65 immunostaining, indicative of NFKB blockage in the area surrounding the needle tip. NFKB blockage induced decreased neuronal survival and induced a further retraction in neuronal dendrites in brain cortex compared with animals that were also exposed to IH but received only vehicle. Our results showed that NFKB activation is necessary for neuronal survival to IH exposure. Further studies are necessary to confirm if the observed NFKB dependence of neuronal survival is a consequence of neuro-glial interaction mediated by S100B-RAGE. Grants CONICET PIP6063, PIP1728, PICT jovenes 33735, IBRO RHF