Hermann Gerlinda E, Tovar C Amy, Rogers Richard C
Laboratory of Autonomic Neuroscience, Pennington Biomedical Research Center, 6400 Perkins Road, Baton Rouge, LA 70808, USA.
Brain Res. 2003 Jun 20;976(1):69-74. doi: 10.1016/s0006-8993(03)02687-8.
The cytokine tumor necrosis factor alpha (TNF(alpha)) may act within the neural circuitry of the medullary dorsal vagal complex (DVC) to affect changes in gastric function such as gastric stasis, loss of appetite, nausea, and vomiting. The definitive demonstration that endogenously generated TNF(alpha) is acting within the DVC circuitry to affect these changes has been impeded by the lack of an antagonist for TNF(alpha). The present studies used localized central nervous system microinjections of the TNF-adsorbant construct (TNFR:Fc) to specifically neutralize the ability of endogenously produced TNF(alpha) to activate NST neurons. Our studies reveal that TNFR:Fc suppresses induction of cFos normally evoked by TNF(alpha). These results validate our hypothesis that circulating TNF(alpha) may act directly within the DVC to affect gastric function in a variety of pathophysiological states.
细胞因子肿瘤坏死因子α(TNFα)可能在延髓背侧迷走神经复合体(DVC)的神经回路中起作用,以影响胃功能的变化,如胃潴留、食欲不振、恶心和呕吐。由于缺乏TNFα拮抗剂,内源性产生的TNFα在DVC回路中起作用以影响这些变化的明确证据一直受到阻碍。本研究使用TNF吸附构建体(TNFR:Fc)进行局部中枢神经系统微注射,以特异性中和内源性产生的TNFα激活孤束核(NST)神经元的能力。我们的研究表明,TNFR:Fc抑制了通常由TNFα诱发的cFos的诱导。这些结果验证了我们的假设,即循环中的TNFα可能直接在DVC内起作用,在多种病理生理状态下影响胃功能。