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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.

Type

Journal article

Journal

J Neurosci

Publication Date

15/04/1998

Volume

18

Pages

3059 - 3072

Keywords

Age Factors, Animals, Axotomy, Drosophila Proteins, Electrophysiology, Ganglia, Spinal, Glial Cell Line-Derived Neurotrophic Factor, Glial Cell Line-Derived Neurotrophic Factor Receptors, Lectins, Male, Nerve Growth Factors, Nerve Tissue Proteins, Neurons, Afferent, Neuroprotective Agents, Nociceptors, Pain, Phosphoric Monoester Hydrolases, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-ret, Rats, Rats, Wistar, Receptor Protein-Tyrosine Kinases, Receptor, trkA, Receptors, Nerve Growth Factor, Sciatic Nerve, Spinal Cord