Helke C J, Adryan K M, Fedorowicz J, Zhuo H, Park J S, Curtis R, Radley H E, Distefano P S
Department of Pharmacology and Neuroscience Program, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814, USA.
J Comp Neurol. 1998 Mar 30;393(1):102-17. doi: 10.1002/(sici)1096-9861(19980330)393:1<102::aid-cne10>3.0.co;2-z.
The receptor-mediated axonal transport of [125I]-labeled neurotrophins by afferent and efferent neurons of the vagus nerve was determined to predict the responsiveness of these neurons to neurotrophins in vivo. [125I]-labeled neurotrophins were administered to the proximal stump of the transected cervical vagus nerve of adult rats. Vagal afferent neurons retrogradely transported [125I]neurotrophin-3 (NT-3), [125I]nerve growth factor (NGF), and [125I]neurotrophin-4 (NT-4) to perikarya in the ipsilateral nodose ganglion, and transganglionically transported [125I]NT-3, [125I]NGF, and [125I]NT-4 to the central terminal field, the nucleus tractus solitarius (NTS). Vagal afferent neurons showed minimal accumulation of [125I]brain-derived neurotrophic factor (BDNF). In contrast, efferent (parasympathetic and motor) neurons located in the dorsal motor nucleus of the vagus and nucleus ambiguus retrogradely transported [125I]BDNF, [125I]NT-3, and [125I]NT-4, but not [125I]NGF. The receptor specificity of neurotrophin transport was examined by applying [125I]-labeled neurotrophins with an excess of unlabeled neurotrophins. The retrograde transport of [125I]NT-3 to the nodose ganglion was reduced by NT-3 and by NGF, and the transport of [125I]NGF was reduced only by NGF, whereas the transport of [125I]NT-4 was significantly reduced by each of the neurotrophins. The competition profiles for the transport of NT-3 and NGF are consistent with the presence of TrkA and TrkC and the absence of TrkB in the nodose ganglion, whereas the profile for NT-4 suggests a p75 receptor-mediated transport mechanism. The transport profiles of neurotrophins by efferent vagal neurons in the dorsal motor nucleus of the vagus and nucleus ambiguus are consistent with the presence of TrkB and TrkC, but not TrkA, in these nuclei. These observations describe the unique receptor-mediated axonal transport of neurotrophins in adult vagal afferent and efferent neurons and thus serve as a template to discern the role of specific neurotrophins in the functions of these visceral sensory and motor neurons in vivo.
通过检测迷走神经传入和传出神经元对[125I]标记神经营养因子的受体介导的轴突运输，来预测这些神经元在体内对神经营养因子的反应性。将[125I]标记的神经营养因子注入成年大鼠横断颈迷走神经的近端残端。迷走神经传入神经元将[125I]神经营养因子-3（NT-3）、[125I]神经生长因子（NGF）和[125I]神经营养因子-4（NT-4）逆行运输至同侧结状神经节的胞体，并经神经节将[125I]NT-3、[125I]NGF和[125I]NT-4运输至中枢终末场，即孤束核（NTS）。迷走神经传入神经元对[125I]脑源性神经营养因子（BDNF）的摄取极少。相比之下，位于迷走神经背运动核和疑核的传出（副交感和运动）神经元逆行运输[125I]BDNF、[125I]NT-3和[125I]NT-4，但不运输[125I]NGF。通过应用过量未标记的神经营养因子与[125I]标记的神经营养因子共同给药，检测神经营养因子运输的受体特异性。NT-3和NGF可减少[125I]NT-3向结状神经节的逆行运输，NGF仅减少[125I]NGF的运输，而每种神经营养因子均可显著减少[125I]NT-4的运输。NT-3和NGF运输的竞争模式与结状神经节中存在TrkA和TrkC以及不存在TrkB一致，而NT-4的模式提示存在p75受体介导的运输机制。迷走神经背运动核和疑核中传出迷走神经元对神经营养因子的运输模式与这些核中存在TrkB和TrkC但不存在TrkA一致。这些观察结果描述了成年迷走神经传入和传出神经元中神经营养因子独特的受体介导的轴突运输，因此可作为一个模板，以识别特定神经营养因子在这些内脏感觉和运动神经元体内功能中的作用。
