Glial Cell Line-Derived Neurotrophic Factor Alters Axon Schwann Cell Units and Promotes Myelination in Unmyelinated Nerve Fibers

Glial cell line-derived neurotrophic factor (GDNF) plays an important role in the development and maintenance of a subset of dorsal root ganglion sensory neurons. We administered high-dose exogenous recombinant human GDNF (rhGDNF) daily to adult rats to examine its effect on unmyelinated axon-Schwann cell units in intact peripheral nerves. In rhGDNF-treated animals, there was a dramatic proliferation in the Schwann cells of unmyelinated fibers, which resulted in the segregation of many unmyelinated axons into a 1:1 relationship with Schwann cells and myelination of normally unmyelinated small axons. This study demonstrates that the administration of high doses of a growth factor to adult rats can change the phenotype of nerve fibers from unmyelinated to myelinated.