Adenosine and sleep deprivation promote NF-kappaB nuclear translocation in cholinergic basal forebrain

In our investigations related to the homeostatic sleep factor adenosine (AD), we previously demonstrated that the DNA-binding activity of the transcription factor NF-kappaB in rat cholinergic basal forebrain increased following 3 h of sleep deprivation (SD). However, the neurotransmitter nature of the cells and the SD-induced stimuli responsible for NF-kappaB activation were not defined. In this report, we demonstrate, using double labeling immunohistochemistry, that nuclear translocation of NF-kappaB occurs almost exclusively in the cholinergic neurons of the basal forebrain following 3 h of SD. Furthermore, cholinergic basal forebrain microinjection of AD (25 nmol/L) or the A(1) receptor agonist N(6)-cyclo-hexyladenosine (100 nmol/L) induced nuclear translocation of NF-kappaB, thus suggesting that SD-induced increased extracellular concentrations of AD, acting via the A(1) AD receptor, may be responsible for the nuclear translocation of NF-kappaB in cholinergic neurons. Moreover, blocking the nuclear translocation of NF-kappaB by injection of inhibitor peptide, SN50, immediately prior to 6 h SD significantly reduced delta activity (1-4 Hz) during the first two hours of recovery sleep. Together, these data suggest a role in sleep homeostasis for the SD-induced activation of NF-kappaB in cholinergic basal forebrain, and that transcription factor NF-kappaB may code for factor(s) that play a role in sleep homeostasis.