Differential effects of tumor necrosis factor-a and -b on the rat ventromedial hypothalamic neurons in vitro. Katafuchi, Toshihiko, Keisuke Motomura, Shingo Baba, Kazuki Ota, and Tetsuro Hori. Department of Physiology, Kyushu University Faculty of Medicine, Fukuoka, 812 Japan
APStracts 4:0080R, 1997.
The effects of tumor necrosis factor-a (TNF-a) and TNF-b on the spontaneous firing rate of ventromedial hypothalamic (VMH) neurons were examined in rat brain slice preparations. Out of 89 neurons, 36 (40%) showed a decrease in the firing rate to -78.2 4.0% (n=36, mean SEM) of the pre-application level following a bath application of 20 ng/ml (about 1.2 nM) of TNF-a. This response to TNF-a still persisted in a low-Ca2+/high-Mg2+ medium. Six (7%) of the 89 neurons were excited and 47 (53%) were unaffected by TNF-a. The inhibitory responses induced by TNF-a were abolished in a solution containing sodium salicylate (1.9 X 10-8 M). In contrast, TNF-b at a dose of 20 ng/ml (about 1.1 nM) increased the firing rate to +39.2 6.5% (n=11) of the pre-application 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-b. The threshold concentration of TNF-a to alter the VMH neuron activity was lower than that of TNF-b. Heat-inactivated TNFs were without effect. These findings suggest that TNF-a and -b act as neuromodulators in the VMH, at least partly through prostaglandin synthesis, and differentially modulate the VMH neuron activity.

Received 19 August 1996; accepted in final form 22 January 1997.
APS Manuscript Number R492-6.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 20 February 1997