Regulation of NGF-family ligands and receptors in adulthood and senescence: correlation to degenerative and regenerative changes in cutaneous innervation

During development, a highly differential neurotrophin dependency is report ed for various types of nerve endings in the whisker follicle. To what exte nt these dependencies extend and play a role in adulthood is largely unreso lved. We show here, using in situ hybridization and immunohistochemistry th at the expression of neurotrophins and trk/p75 receptors persists in adulth ood. As suggested by their expression profiles, many classes of cutaneous n erve endings disclose similar ligand-receptor dependencies in adult animals as during development, while other populations appear to switch their depe ndency. Furthermore, our data suggest that sensory endings that have a high turnover due to mechanical wear and tear, e.g. Merkel cell-neurite complex es at the level of ring sinus show a more complex ligand-receptor expressio n phenotype than do endings with a less vulnerable location, e.g. the Merke l cell-neurite complexes at the rete ridge collar. Thus, neurotrophin-3 (NT 3)/trkA signalling is suggested to be important for a continuous terminal p lasticity of Merkel cell-neurite complexes at the level of ring sinus in ad ulthood. Evidence supporting a role for neurotrophin signalling in maintain ing the adult cutaneous innervation also comes from the close correlation b etween altered ligand-receptor expression(s) and axonal/terminal aberration s in senescence. Thus, an ageing-related decrease in target neurotrophin ex pression, notably NT3 and NT4, results in a site-specific loss of sensory t erminals concomitant with an aberrant growth of regenerating/sprouting axon s into new target fields. Ageing of the cutaneous innervation, manifested i n degenerative and regenerative events, seems strongly associated with chan ges in neurotrophic interactions between sensory neurons and target tissues .