Inhibition of axoplasmic transport in the rat vagus nerve alters the numbers of neuropeptide and tyrosine hydroxylase messenger RNA-containing and immunoreactive visceral afferent neurons of the nodose ganglion

Abstract Previous work showed that axotomy-induced deafferentation of the placode-derived visceral afferent neurons of the nodose ganglion altered their expression of some neuropeptides and tyrosine hydroxylase. The present studies were designed to selectively evaluate the loss of axonal transport on the numbers of vasoactive intestinal polypeptide, tyrosine hydroxylase, and calcitonin gene-related peptide mRNA-containing and immunoreactive neurons in the nodose ganglion of the adult rat. Vinblastine (0.15 mM) application to the cervical vagus nerve was used to block axonal tranport between ganglionic perikarya and peripheral targets. In situ hybridization histochemistry with 35 S-labeled oligonucleotide probes was used to both quantify the number of mRNA-containing neurons and to assess the density of mRNA expression per neuron, and immunocytochemistryk was used to visualize the number of immunoreactive neurons. The efficacy of vinblastine to inhibit axonal transport was verified by evaluating the build-up of calcitonin gene-related peptide immunoreactive in the vagus nerve immediately rostral to the site of drug application. The absence of vinblastine-induced neuronal damage was verified by the relative absence of degenerating nerves in the vagus nerve caudal to the site of drug application. Vinblastine treatment of the vagus nerve increased the numbers of vasoactive intestinal peptide mRNA-containing neurons and vasoactive intestinal peptide-immunoreactive neurons in the nodose ganglion at three, seven and 14 days, and increased the numbers of calcitonin gene-related peptide mRNA-containing and calcitonin gene-related peptide-immunoreactive neurons in the nodose ganglion at one, three and seven days. The average labeling density of vasoactive intestinal peptide mRNA-containing neurons was also increased following vinblastine treatment. Vinblastine treatment of the cervical vagus nerve, however, led to the appearance of low-labeling density calcitonin gene-related peptide mRNA-neurons and resulted in reduction of the average labeling density for calcitonin gene-related peptide mRNA-containing neurons. In contrast, application of vinblastine to the cervical vagus nerve, decreased the number of tyrosine hydroxylase mRNA-containing and tyrosine hydroxylase-immunoreactive neurons in the nodose ganglion. In summary, inhibition of the axoplasmic transport between the periphery and the visceral sensory perikarya appeared to alter vasoactive intestinal peptide, calcitonin gene-related peptide, and tyrosine hydroxylase expression and content in visceral sensory neurons of the nodose ganglion. These data suggest the presence of an axonally transported influence on the regulation of neuropeptide and neurotransmitter enzyme synthesis in mature placode-derived visceral sensory neurons.