TNF-α-induced c-Fos generation in the nucleus of the solitary tract is blocked by NBQX and MK-801

Abstract

Previous studies have shown that identified neurons of the nucleus of the solitary tract (NST) are excited by the cytokine tumor necrosis factor-α (TNF-α). Vagal afferent connections with the NST are predominantly glutaminergic. Therefore, we hypothesized that TNF-α effects on NST neurons may be via modulation of glutamate neurotransmission. The present study used activation of the immediate early gene product c-Fos as a marker for neuronal activation in the NST. c-Fos expression was evaluated after microinjections of TNF-α in the presence or absence of either the α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor antagonist 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide disodium (NBQX) or the N-methyl-d- aspartate (NMDA) antagonist MK-801. To assess the specificity of the interaction between TNF-α and glutamate, c-Fos expression was also evaluated after injection of oxytocin (OT) (which has a direct excitatory effect in this area of the brain stem) in the presence and absence of NBQX or MK-801. c-Fos labeling was significantly increased in the NST after TNF-α exposure. Coinjection of either NBQX or MK-801 with TNF-α prevented significant c-Fos induction in the NST. Microinjections of OT also induced significant NST c-Fos elevation, but this expression was unaffected by coinjection of either antagonist with OT. These data lead us to conclude that TNF-α activation of NST neurons depends on glutamate and such an interaction is not generalized to all agonists that act on the NST.