Nuclear factor-kappa B-like activity increases in murine cerebral cortex after sleep deprivation

Several well-defined sleep regulatory substances, e.g., interleukin-1 beta, activate the heterodimeric transcription factor nuclear factor-kappa B (NF -kappa B). Several substances that inhibit sleep, e.g., interleukin-4, inhi bit NF-kappa B activation. NF-kappa B activation promotes production of sev eral additional substances thought to be involved in sleep regulation, e.g. , nitric oxide. We investigated, therefore, whether there are diurnal rhyth ms of NF-kappa B activation in brain and changes in the activation after sl eep deprivation. Mice were kept on a 12:12-h light-dark cycle. In one exper iment, groups of mice were killed every 3 h across the 24-h cycle. In anoth er experiment, mice were killed at 1500 after 6 h of sleep deprivation, and a group of control mice were killed at the same time. Nuclear proteins wer e extracted from each brain tissue sample, and NF-kappa B-like activity was determined with an electrophoretic mobility shift assay. In cerebral corte x, but not other areas of brain, there was a diurnal rhythm in NF-kappa B-l ike activation; highest levels were found during the light period. NF-kappa B-like activation was higher in cerebral cortex after sleep deprivation co mpared with values obtained from control mice. The results are consistent w ith the hypothesis that sleep regulation involves multiple gene events, som e of which include enhanced production of sleep regulatory substances, the actions of which involve NF-kappa B activation.