Axonal transport of neurotrophins by visceral afferent and efferent neurons of the vagus nerve of the rat

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. J. Comp. Neurol. 393:102–117, 1998. Published 1998 Wiley-Liss, Inc.

1 This article is a US government work and, as such, is in the public domain in the United States of America.