Hermann Gerlinda E, Hebert Sadie L, Van Meter Montina J, Holmes Gregory M, Rogers Richard C
Laboratory of Autonomic Neuroscience, Pennington Biomedical Research Center, Louisiana State University, 6400 Perkins Rd., Baton Rouge, LA 70808, USA.
Brain Res. 2004 Apr 9;1004(1-2):156-66. doi: 10.1016/j.brainres.2003.11.078.
Tumor necrosis factor alpha (TNF(alpha)) is a potent modulator of autonomic reflex mechanisms that control the stomach. Evidence suggests that TNF(alpha) action directly on vago-vagal reflex control circuits causes the autonomic misregulation of digestion manifested as gastrointestinal stasis, nausea, and emesis associated with illness. Neurophysiological studies indicated that TNF(alpha) may have effects on vagal afferents in the solitary nucleus, as well as neurons of the solitary nucleus (NST) and dorsal motor nucleus (DMN) of the vagus. The aim of this study was to determine the location of the TNFR1 receptor (p55) in the medulla using immunocytochemical methods. We devised a technique for localizing the p55 receptor using heat-induced antigen recovery in fixed tissue sections. This protocol allowed us to demonstrate that dense p55-immunoreactivity (p55-ir) is constitutively present on central (but not peripheral) vagal afferents in the solitary tract (ST) and nucleus; p55-ir is also present on afferents entering the spinal trigeminal nucleus. Unilateral supra-nodose vagotomy eliminated p55-ir from ipsilateral central vagal afferents. Virtually all neurons in the brainstem appeared to express p55-ir at a low level, i.e., just above background. However, vagotomy caused a dramatic up-regulation of p55-ir in vagal motor neurons. This increase in p55-ir in axotomized neurons may play a pivotal role in the connection between the occurrence of the injury and the initiation of apoptotic processes resulting in elimination of damaged neurons.
肿瘤坏死因子α（TNFα）是控制胃部自主反射机制的强效调节剂。有证据表明，TNFα直接作用于迷走-迷走反射控制回路会导致消化自主调节异常，表现为胃肠道淤滞、恶心和与疾病相关的呕吐。神经生理学研究表明，TNFα可能对孤束核中的迷走传入神经以及迷走神经的孤束核（NST）和背运动核（DMN）中的神经元有影响。本研究的目的是使用免疫细胞化学方法确定延髓中TNFR1受体（p55）的位置。我们设计了一种在固定组织切片中利用热诱导抗原修复来定位p55受体的技术。该方案使我们能够证明，在孤束（ST）和核中的中枢（而非外周）迷走传入神经上持续存在密集的p55免疫反应性（p55-ir）；p55-ir也存在于进入三叉神经脊束核的传入神经上。单侧结上迷走神经切断术消除了同侧中枢迷走传入神经上的p55-ir。实际上，脑干中的所有神经元似乎都以低水平表达p55-ir，即略高于背景水平。然而，迷走神经切断术导致迷走运动神经元中p55-ir显著上调。轴突切断的神经元中p55-ir的这种增加可能在损伤的发生与导致受损神经元消除的凋亡过程启动之间的联系中起关键作用。
