Nuclear factor-κB-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, inhibit NF-kappa B activation. NF-kappa B activation promotes production of several additional substances thought to be involved in sleep regulation, e.g., nitric oxide. We investigated, therefore, whether there are diurnal rhythms of NF-kappa B activation in brain and changes in the activation after sleep deprivation. Mice were kept on a 12:12-h light-dark cycle. In one experiment, groups of mice were killed every 3 h across the 24-h cycle. In another 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 were extracted from each brain tissue sample, and NF-kappa B-like activity was determined with an electrophoretic mobility shift assay. In cerebral cortex, but not other areas of brain, there was a diurnal rhythm in NF-kappa B-like activation; highest levels were found during the light period. NF-kappa B-like activation was higher in cerebral cortex after sleep deprivation compared with values obtained from control mice. The results are consistent with the hypothesis that sleep regulation involves multiple gene events, some of which include enhanced production of sleep regulatory substances, the actions of which involve NF-kappa B activation.