A distinct subgroup of small DRG cells express GDNF receptor components and GDNF is protective for these neurons after nerve injury.
Several lines of evidence suggest that neurotrophin administration may be of some therapeutic benefit in the treatment of peripheral neuropathy. However, a third of sensory neurons do not express receptors for the neurotrophins. These neurons are of small diameter and can be identified by the binding of the lectin IB4 and the expression of the enzyme thiamine monophosphatase (TMP). Here we show that these neurons express the receptor components for glial-derived neurotrophic factor (GDNF) signaling (RET, GFRalpha-1, and GFRalpha-2). In lumbar dorsal root ganglia, virtually all IB4-labeled cells express RET mRNA, and the majority of these cells (79%) also express GFRalpha-1, GFRalpha-2, or GFRalpha-1 plus GFRalpha-2. GDNF, but not nerve growth factor (NGF), can prevent several axotomy-induced changes in these neurons, including the downregulation of IB4 binding, TMP activity, and somatostatin expression. GDNF also prevents the slowing of conduction velocity that normally occurs after axotomy in a population of small diameter DRG cells and the A-fiber sprouting into lamina II of the dorsal horn. GDNF therefore may be useful in the treatment of peripheral neuropathies and may protect peripheral neurons that are refractory to neurotrophin treatment.
Bennett
D L
DL
Department of Physiology, United Medical and Dental Schools (St. Thomas' Campus), London, SE1 7EH, United Kingdom.
Michael
G J
GJ
Ramachandran
N
N
Munson
J B
JB
Averill
S
S
Yan
Q
Q
McMahon
S B
SB
Priestley
J V
JV
D000367:Age Factors; D000818:Animals; D019771:Axotomy; D029721:Drosophila Proteins; D004594:Electrophysiology; D005727:Ganglia, Spinal / Q000737:chemistry / Q000166:cytology* / Q000201:enzymology; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D037102:Lectins; D008297:Male; D009414:Nerve Growth Factors / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000494:pharmacology; D009475:Neurons, Afferent / Q000737:chemistry* / Q000187:drug effects / Q000201:enzymology; D018696:Neuroprotective Agents / Q000494:pharmacology; D009619:Nociceptors / Q000502:physiology; D010146:Pain / Q000503:physiopathology; D010744:Phosphoric Monoester Hydrolases / Q000032:analysis / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000378:metabolism / Q000502:physiology*; D051096:Proto-Oncogene Proteins c-ret; D051381:Rats; D017208:Rats, Wistar; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis / Q000378:metabolism / Q000502:physiology*; D020917:Receptor, trkA; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D012584:Sciatic Nerve / Q000737:chemistry / Q000201:enzymology / Q000601:surgery; D013116:Spinal Cord / Q000737:chemistry / Q000166:cytology / Q000201:enzymology
D029721:Drosophila Proteins; C495041:Gdnf protein, rat; C494989:Gfra1 protein, rat; C494992:Gfra2 protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D037102:Lectins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D011518:Proto-Oncogene Proteins; D017475:Receptors, Nerve Growth Factor; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA; C416649:Ret protein, Drosophila; C495001:Ret protein, rat; C022734:thiamine monophosphatase; D010744:Phosphoric Monoester Hydrolases