title: Axonal transport of neurotrophins by visceral afferent and efferent neurons of the vagus nerve of the rat.
abstract: 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.
authors.affiliation: Department of Pharmacology and Neuroscience Program, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814, USA. chelke@usuhs.mil
authors.forename: C J
authors.initials: CJ
authors.lastname: Helke
authors.forename: K M
authors.initials: KM
authors.lastname: Adryan
authors.forename: J
authors.initials: J
authors.lastname: Fedorowicz
authors.forename: H
authors.initials: H
authors.lastname: Zhuo
authors.forename: J S
authors.initials: JS
authors.lastname: Park
authors.forename: R
authors.initials: R
authors.lastname: Curtis
authors.forename: H E
authors.initials: HE
authors.lastname: Radley
authors.forename: P S
authors.initials: PS
authors.lastname: Distefano
mesh_terms: D000818:Animals; D001370:Axonal Transport / Q000502:physiology*; D015870:Gene Expression; D007457:Iodine Radioisotopes; D008297:Male; D009414:Nerve Growth Factors / Q000493:pharmacokinetics*; D009475:Neurons, Afferent / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D009476:Neurons, Efferent / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000493:pharmacokinetics; D020933:Neurotrophin 3; D009620:Nodose Ganglion / Q000166:cytology* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley / Q000502:physiology*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D020801:Receptor, Ciliary Neurotrophic Factor; D020800:Receptor, Nerve Growth Factor; D020917:Receptor, trkA; D020812:Receptor, trkC; D017475:Receptors, Nerve Growth Factor / Q000235:genetics; D017552:Solitary Nucleus / Q000166:cytology / Q000378:metabolism; D014628:Vagotomy
chemical_list: D007457:Iodine Radioisotopes; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; D020933:Neurotrophin 3; D011518:Proto-Oncogene Proteins; D020801:Receptor, Ciliary Neurotrophic Factor; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA; D020812:Receptor, trkC; C073922:neurotrophin 4