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PMID: 9526023 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

A distinct subgroup of small DRG cells express GDNF receptor components and GDNF is protective for these neurons after nerve injury.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 18 ·No. 8 ·1998-04-15 ·Pages 3059-72

Bennett DL, Michael GJ, Ramachandran N, Munson JB, Averill S, Yan Q, McMahon SB, Priestley JV

Abstract

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.

MeSH Terms
Age Factors Animals Axotomy Drosophila Proteins Electrophysiology Ganglia, Spinal/chemistry,cytology,enzymology Glial Cell Line-Derived Neurotrophic Factor Glial Cell Line-Derived Neurotrophic Factor Receptors Lectins Male Nerve Growth Factors/pharmacology Nerve Tissue Proteins/pharmacology Neurons, Afferent/chemistry,drug effects,enzymology Neuroprotective Agents/pharmacology Nociceptors/physiology Pain/physiopathology Phosphoric Monoester Hydrolases/analysis,metabolism Proto-Oncogene Proteins/analysis,metabolism,physiology Proto-Oncogene Proteins c-ret Rats Rats, Wistar Receptor Protein-Tyrosine Kinases/analysis,metabolism,physiology Receptor, trkA Receptors, Nerve Growth Factor/metabolism Sciatic Nerve/chemistry,enzymology,surgery Spinal Cord/chemistry,cytology,enzymology
Chemicals
Drosophila Proteins Gdnf protein, rat Gfra1 protein, rat Gfra2 protein, rat Glial Cell Line-Derived Neurotrophic Factor Glial Cell Line-Derived Neurotrophic Factor Receptors Lectins Nerve Growth Factors Nerve Tissue Proteins Neuroprotective Agents Proto-Oncogene Proteins Receptors, Nerve Growth Factor Proto-Oncogene Proteins c-ret Receptor Protein-Tyrosine Kinases Receptor, trkA Ret protein, Drosophila Ret protein, rat thiamine monophosphatase Phosphoric Monoester Hydrolases
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Bennett D L
Department of Physiology, United Medical and Dental Schools (St. Thomas' Campus), London, SE1 7EH, United Kingdom.
Michael G J
Ramachandran N
Munson J B
Averill S
Yan Q
McMahon S B
Priestley J V
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
0270-6474
Published
1998-04-15
Pages
3059-72
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6792585
Subset
IM
External Links
PubMed source PMC Full Text View journal details
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