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

Previous work showed that axotomy-induced deafferentation of the placo de-derived visceral afferent neurons of the nodose ganglion altered th eir expression of some neuropeptides and tyrosine hydroxylase. The pre sent studies were designed to selectively evaluate the loss of axonal transport on the numbers of vasoactive intestinal polypeptide, tyrosin e hydroxylase, and calcitonin gene-related peptide mRNA-containing and immunoreactive neurons in the nodose ganglion of the adult rat. Vinbl astine (0.15 mM) application to the cervical vagus nerve was used to b lock axonal transport between ganglionic perikarya and peripheral targ ets. In situ hybridization histochemistry with S-35-labeled oligonucle otide probes was used to both quantify the number of mRNA-containing n eurons and to assess the density of mRNA expression per neuron, and im munocytochemistry was used to visualize the number of immunoreactive n eurons. The efficacy of vinblastine to inhibit axonal transport was ve rified by evaluating the build-up of calcitonin gene-related peptide i mmunoreactive in the vagus nerve immediately rostral to the site of dr ug 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 peptid e mRNA-containing neurons and vasoactive intestinal peptide-immunoreac tive neurons in the nodose ganglion at three, seven and 14 days, and i ncreased the numbers of calcitonin gene-related peptide mRNA-containin g and calcitonin gene-related peptide-immunoreactive neurons in the no dose ganglion at one, three and seven days. The average labeling densi ty of vasoactive intestinal peptide mRNA-containing neurons was also i ncreased 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 r eduction of the average labeling density for calcitonin gene-related p eptide mRNA-containing neurons. In contrast, application of vinblastin e to the cervical vagus nerve, decreased the number of tyrosine hydrox ylase mRNA-containing and tyrosine hydroxylase-immunoreactive neurons in the nodose ganglion. In summary, inhibition of the axoplasmic trans port between the periphery and the visceral sensory perikarya appeared to alter vasoactive intestinal peptide, calcitonin gene-related pepti de, and tyrosine hydroxylase expression and content in visceral sensor y neurons of the nodose ganglion. These data suggest the presence of a n axonally transported influence on the regulation of neuropeptide and neurotransmitter enzyme synthesis in mature placode-derived visceral sensory neurons.