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.
Höke
Ahmet
A
Johns Hopkins Hospital, Department of Neurology, Baltimore, Maryland 21205, and Amgen, Inc., Thousand Oaks, California 91320-1799, USA. ahoke@jhmi.edu
Ho
Tony
T
Crawford
Thomas O
TO
LeBel
Carl
C
Hilt
Dana
D
Griffin
John W
JW
D000818:Animals; D001369:Axons / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D004305:Dose-Response Relationship, Drug; D005727:Ganglia, Spinal / Q000166:cytology; D051100:Glial Cell Line-Derived Neurotrophic Factor; D008297:Male; D009186:Myelin Sheath / Q000378:metabolism*; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects / Q000378:metabolism; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D012583:Schwann Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D012584:Sciatic Nerve / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D011994:Recombinant Proteins