Differential effects of tumor necrosis factor-alpha and -beta on rat ventromedial hypothalamic neurons in vitro

The effects of tumor necrosis factor (TNF)-alpha and -beta on the spontaneous firing rate of ventromedial hypothalamic (VMH) neurons were examined in rat brain slice preparations. Of 89 neurons, 36 (40%) showed a decrease in the firing rate to -78.2 +/- 4.0% (n = 36, mean +/- SE) of the preapplication level after a bath application of 20 ng/ml (approximately 1.2 nM) of TNF-alpha. This response to TNF-alpha still persisted in a low-Ca2+, high-Mg2+ medium. Six (7%) of the 89 neurons were excited and 47 (53%) were unaffected by TNF-alpha. The inhibitory responses induced by TNF-alpha were abolished in a solution that contained sodium salicylate (1.9 x 10(-8)M). In contrast, TNF-beta at a dose of 20 ng/ml (approximately 1.1 nM) increased the firing rate to +39.2 +/- 6.5% (n = 11) of the preapplication level in 11 (24.5%) of 45 VMH neurons. Two of the 45 neurons (4.5%) were inhibited and 32 (71%) were unaffected by TNF-beta. The threshold concentration of TNF-alpha to alter the VMH neuron activity was lower than that of TNF-beta. Heat-inactivated TNFs were without effect. These findings suggest that TNF-alpha and -beta act as neuromodulators in the VMH, at least partly through prostaglandin synthesis, and differentially modulate the VMH neuron activity.