title: Bacterial endotoxin induces fos immunoreactivity in primary afferent neurons of the vagus nerve.
abstract: Subdiaphragmatic vagotomy inhibits brain-mediated illness responses to peripherally administered bacterial endotoxin, including fever, hyperalgesia, sickness behavior, and activation of the hypothalamic-pituitary-adrenal axis. However, direct evidence implicating vagal afferents specifically in conveying information about peripheral immune activation to the brain is still lacking. This study assessed whether (1) endotoxin induces the expression of the functional activation marker Fos in the vagal sensory ganglia, and (2) vagotomy abrogates endotoxin-induced Fos expression in these ganglia. Male rats, which had previously received vagotomy or sham surgery, were injected intraperitoneally or intravenously with either endotoxin or saline. Fos immunolabeling was absent in saline-treated rats. In contrast, scattered cells within the vagal sensory ganglia showed Fos immunoreactivity after both intraperitoneal and intravenous endotoxin administration in sham-operated rats. Vagotomy abolished Fos expression after intraperitoneal endotoxin administration, whereas after intravenous administration Fos expression was strongly attenuated, but not eliminated. These findings implicate vagal afferents as a potential signaling pathway to brain regions that generate illness responses to pro-inflammatory mediators.
authors.affiliation: Department of Psychology, University of Colorado, Boulder, Colo., USA gaykema@psch.colorado.edu
authors.forename: R P
authors.initials: RP
authors.lastname: Gaykema
authors.forename: L E
authors.initials: LE
authors.lastname: Goehler
authors.forename: F J
authors.initials: FJ
authors.lastname: Tilders
authors.forename: J G
authors.initials: JG
authors.lastname: Bol
authors.forename: M
authors.initials: M
authors.lastname: McGorry
authors.forename: M
authors.initials: M
authors.lastname: Fleshner
authors.forename: S F
authors.initials: SF
authors.lastname: Maier
authors.forename: L R
authors.initials: LR
authors.lastname: Watkins
mesh_terms: D000818:Animals; D005930:Glossopharyngeal Nerve / Q000033:anatomy & histology; D007150:Immunohistochemistry; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009475:Neurons, Afferent / Q000737:chemistry / Q000276:immunology*; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis* / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014628:Vagotomy; D014630:Vagus Nerve / Q000033:anatomy & histology / Q000737:chemistry / Q000187:drug effects / Q000276:immunology*
chemical_list: D008070:Lipopolysaccharides; D016760:Proto-Oncogene Proteins c-fos