MK-801 PREVENTS CYANIDE-INDUCED CHANGES OF FOS LEVELS IN RAT-BRAIN

The effect of acute cyanide intoxication on levels of transcriptional regulatory proteins Fos and c-Jun in rat cortex, hippocampus, cerebell um and brain stem was studied. Western blot analysis showed a differen tial effect of cyanide on Fos levels in the selected brain areas. The most prominent changes were seen 60 min. following ip. injection of KC N in all brain areas except the brain stem, which showed the maximal c hange 120 min. following cyanide. Fos levels were doubled in cortex an d cerebellum and decreased to below 70% of the control levels in hippo campus. Levels of c-Jun were not altered 60 min. following cyanide tre atment. Pretreatment with the NMDA receptor antagonist, MK-801, preven ted the cyanide-induced changes of Fos. The differential effect of cya nide on Fos levels in different brain areas and the blockade of these changes by MK-801 suggest involvement of multiple neuronal pathways, i ncluding the excitatory amino acid (EAA) neurotransmitter system. It i s concluded that cyanide alters levels of the transcriptional regulato ry protein Fos through activation of the EAA neurotransmitter system a nd, thus, may affect gene expression in neuronal or glia cells.