PLASTICITY OF NEUROPEPTIDE-Y IN THE RAT SUPERIOR CERVICAL-GANGLION INRESPONSE TO NERVE LESION

Axotomy of the rat superior cervical ganglion results in a two-fold in crease of neuropeptide tyrosine as determined by radioimmunoassay.(9) On the other hand, treatment of sympathetic neuron cultures with leuke mia inhibitory factor, a cytokine that is known to be involved in the up-regulation of galanin after axotomy in vivo, decreases neuropeptide tyrosine messenger RNA.(21) These, apparently contradictory findings, prompted us to investigate the regulation of neuropeptide tyrosine in the axotomized superior cervical ganglion in vivo. For comparison, th e regulation of galanin was examined under the same conditions. Compar ed to control ganglia, the number of neuropeptide tyrosine-positive ce ll bodies decreased while the density of immunoreactive neuronal proce sses increased one week after transection of the major postganglionic nerves. The nerve fibres were identified as axons by the absence of MA P2, a somatodendritic marker protein. They extended into both carotid nerves and ramified at the lesion site. In situ hybridization revealed that, although the number of neuropeptide tyrosine messenger RNA-posi tive neurons was not different from controls, the average grain densit y/neuron decreased by 40%. When axotomized ganglia were decentralized simultaneously, a three-fold elevation of neuropeptide tyrosine immuno reactivity was detectable by radioimmunoassay and an additional increa se in numerical density of neuropeptide tyrosine-immunoreactive nerve fibres was observed. Levels of neuropeptide tyrosine messenger RNA wer e significantly reduced within postganglionic neurons. This synergisti c effect of combined axotomy and decentralization on peptide content w as also detected for the neuropeptide galanin that, in contrast to neu ropeptide tyrosine, is induced by axotomy or decentralization on prote in and messenger RNA level. Therefore, while neuropeptide tyrosine mes senger RNA is reduced in axotomized ganglia (most likely in response t o leukemia inhibitory factor), the peptide accumulates in axonal proce sses resulting in increased peptide levels as determined by radioimmun oassay. (C) 1997 IBRO.