DEXAMETHASONE ATTENUATES NF-KAPPA-B DNA-BINDING ACTIVITY WITHOUT INDUCING I-KAPPA-B LEVELS IN RAT-BRAIN IN-VIVO

This investigation tested if glucocorticoid hormones modulate activati on of the NF-KB transcription factor in rat brain in vivo. Dexamethaso ne (2 mg/kg) administration decreased NF-KB DNA binding in cerebral co rtex and hippocampus nuclear extracts, maximally at 3-6 h after dexame thasone, followed by recovery at 24 h. Dexamethasone did not inhibit N F-KB by increasing the level of the inhibitory protein I kappa B alpha , as occurs in some peripheral cells, but instead lowered I kappa B al pha levels. Direct protein-protein inhibition by glucocorticoids was i ndicated by co-precipitation of glucocorticoid receptors with the p65 NF-KB subunit. Thus, glucocorticoids inhibit NF-kappa B DNA binding in rat brain, apparently by complexing with NF-kappa B subunits, which m ay contribute to the detrimental effects of glucocorticoids on neurona l function associated with oxidative stress and excitotoxicity.