TNFalpha-stimulation of cFos-activation of neurons in the solitary nucleus is suppressed by TNFR:Fc adsorbant construct in the dorsal vagal complex.
The cytokine tumor necrosis factor alpha (TNF(alpha)) may act within the neural circuitry of the medullary dorsal vagal complex (DVC) to affect changes in gastric function such as gastric stasis, loss of appetite, nausea, and vomiting. The definitive demonstration that endogenously generated TNF(alpha) is acting within the DVC circuitry to affect these changes has been impeded by the lack of an antagonist for TNF(alpha). The present studies used localized central nervous system microinjections of the TNF-adsorbant construct (TNFR:Fc) to specifically neutralize the ability of endogenously produced TNF(alpha) to activate NST neurons. Our studies reveal that TNFR:Fc suppresses induction of cFos normally evoked by TNF(alpha). These results validate our hypothesis that circulating TNF(alpha) may act directly within the DVC to affect gastric function in a variety of pathophysiological states.
Hermann
Gerlinda E
GE
Laboratory of Autonomic Neuroscience, Pennington Biomedical Research Center, 6400 Perkins Road, Baton Rouge, LA 70808, USA. hermange@pbrc.edu
Tovar
C Amy
CA
Rogers
Richard C
RC
D000818:Animals; D000068800:Etanercept; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000494:pharmacology*; D007276:Injections, Intraventricular; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects* / Q000378:metabolism; D008845:Microinjections; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D051381:Rats; D020318:Rats, Long-Evans; D018124:Receptors, Tumor Necrosis Factor / Q000008:administration & dosage; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D017552:Solitary Nucleus / Q000187:drug effects* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000494:pharmacology / Q000502:physiology*; D014630:Vagus Nerve / Q000187:drug effects* / Q000378:metabolism
D007074:Immunoglobulin G; D016760:Proto-Oncogene Proteins c-fos; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha; D000068800:Etanercept