Regulation of neuropeptide expression in sympathetic neurons. Paracrine and retrograde influences

Sympathetic neurons and other peripheral neurons exhibit a great deal of plasticity in their neuropeptide phenotype in adulthood. In this review, two phenotypes have been described in detail: that of normal sympathetic neurons and that of axotomized neurons. Two factors produced by nonneuronal cells, LIF and NGF, determine which of these phenotypes is expressed. Under normal conditions, the neurons receive NGF primarily, if not exclusively, from the target tissues they innervate. Prior to surgery, the nonneuronal cells within the ganglion and nerve tract express little, if any, LIF. This milieu favors the expression of NPY and suppresses the expression of VIP, galanin, and substance P (Fig. 6). After axotomy, however, this situation is reversed. The neuronal cell bodies are deprived of target-derived NGF and are exposed to LIF both within the ganglion and at the site of the injury (Fig 6). Both the removal of NGF and the exposure to LIF inhibit NPY expression, while promoting the expression of VIP and galanin. Expression of substance P after axotomy occurs primarily, if not entirely, because of the effects of LIF, with the removal of NGF playing no obvious role in the regulation of this peptide.