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.
Ramesh
Vijay
V
Department of Psychiatry, VA Boston Healthcare System and Harvard Medical School, West Roxbury, Massachusetts, USA.
Thatte
Hemant S
HS
McCarley
Robert W
RW
Basheer
Radhika
R
D021581:Active Transport, Cell Nucleus; D000241:Adenosine / Q000494:pharmacology / Q000502:physiology*; D058907:Adenosine A1 Receptor Agonists; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D002795:Choline O-Acetyltransferase / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D008845:Microinjections; D016328:NF-kappa B / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology; D016548:Prosencephalon / Q000378:metabolism*; D051381:Rats; D020318:Rats, Long-Evans; D043682:Receptor, Adenosine A1 / Q000502:physiology; D015398:Signal Transduction; D012890:Sleep / Q000502:physiology; D012892:Sleep Deprivation; D014851:Wakefulness
D058907:Adenosine A1 Receptor Agonists; D016328:NF-kappa B; D010455:Peptides; D043682:Receptor, Adenosine A1; C118258:SN50 peptide; D002795:Choline O-Acetyltransferase; D000241:Adenosine