IBCN   20355
INSTITUTO DE BIOLOGIA CELULAR Y NEUROCIENCIA "PROFESOR EDUARDO DE ROBERTIS"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Inhibition of NF-kB by Sulfazalasin in animals subjected to intermittent hypoxia
Autor/es:
ANGELO MF; AVILES REYES RX; VILLAREAL A; UNSAIN N; BARKER PA; RAMOS AJ
Lugar:
San Diego EEUU
Reunión:
Congreso; Society for Neuroscience; 2010
Resumen:
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 heath in hippocampus and brain cortex, two anatomical areas related to the cognitive impairments observed in human patients. Surprisingly, a significant neuronal survival was observed after longer exposure to IH (Aviles-Reyes et al., 2010, J. Neurochem 112:854). In order to analyze NFkB transcription factor involvement in the neuronal survival after IH, we exposed NFêB reporter mice or wistar rats to IH cycles (alternating 10% - 21% O2) every 6 min during 8h per day during 3 consecutive days. A separated set of animals was cannulated 3 days before the IH exposure, allowed to recover from surgery and received an intrahippocampal infusion of NFkB blocker sulfasalazine (SFZ) (1uL; 1.25mM) or vehicle at the beginning of each day of IH exposure. On the 4th day, animals were deeply anesthetized and fixed by perfusion for immunocytochemistry or brains dissected for RT-PCR studies. IH exposure increased NFêB transcriptional activity as judged from NFêB reporter transgenic mice that presented increased NFêB dependent X-gal activity. XIAP, cIAP-2 and IêB mRNAs were significantly increased after 3 days of IH exposure. In vivo blockage of NFêB activation with intrahippocampal SFZ infusion resulted in a persistence of cytoplasmic p65 subunit immunostaining in the hippocampal pyramidal cell layer, indicative of the blockage of NFêB nuclear traslocation, and decreased the number of degenerating neurons as shown by a reduction of neurons with atypical nuclear morphology by NeuN immunostaining. Our results showed that NFêB dependent transcriptional activity is increased after IH exposure. However, NFêB blockage in vivo improved neuronal survival thus showing that NFêB may have = main role in the initial neuronal degeneration induced by IH, while NFêB prosurvival effects are probably evidenced at later time points