The effects of tumor necrosis factor (TNF)-α and -β 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 (~1.2 nM) of TNF- α. This response to TNF-α still persisted in a low-Ca2+, high-Mg2+ medium. Six (7%) of the 89 neurons were excited and 47 (53%) were unaffected by TNF-α. The inhibitory responses induced by TNF-α were abolished in a solution that contained sodium salicylate (1.9 x 10-8 M). In contrast, TNF-β at a dose of 20 ng/ml (~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-β. The threshold concentration of TNF-α to alter the VMH neuron activity was lower than that of TNF-β. Heat-inactivated TNFs were without effect. These findings suggest that TNF-α and -β act as neuromodulators in the VMH, at least partly through prostaglandin synthesis, and differentially modulate the VMH neuron activity.
|Journal||American Journal of Physiology - Regulatory Integrative and Comparative Physiology|
|Issue number||6 41-6|
|Publication status||Published - Aug 2 1997|
All Science Journal Classification (ASJC) codes
- Physiology (medical)