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Am J Physiol Regul Integr Comp Physiol 272: R1966-R1971, 1997;
0363-6119/97 $5.00
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AJP - Regulatory, Integrative and Comparative Physiology, Vol 272, Issue 6 1966-R1971, Copyright © 1997 by American Physiological Society

ARTICLES

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

T. Katafuchi, K. Motomura, S. Baba, K. Ota and T. Hori
Department of Physiology, Kyushu University Faculty of Medicine, Fukuoka, Japan.

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.


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[Abstract] [Full Text] [PDF]


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