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The Journal of Neuroscience, April 15, 1998, 18(8):3059-3072

A Distinct Subgroup of Small DRG Cells Express GDNF Receptor Components and GDNF Is Protective for These Neurons after Nerve Injury

David L. H. Bennett¹, Gregory J. Michael², Navin Ramachandran¹, John B. Munson³, Sharon Averill², Qiao Yan⁴, Stephen B. McMahon¹, and John V. Priestley²

¹ Department of Physiology, United Medical and Dental Schools (St. Thomas' Campus), London, SE1 7EH, United Kingdom, ² Department of Anatomy, Queen Mary and Westfield College, London, E1 4NS, United Kingdom, ³ Department of Neuroscience, University of Florida College of Medicine, Gainsville, Florida 32610, and ⁴ Department of Neuroscience, Amgen Inc., Thousand Oaks, California 91320

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, GFR-1, and GFR-2). In lumbar dorsal root ganglia, virtually all IB4-labeled cells express RET mRNA, and the majority of these cells (79%) also express GFR-1, GFR-2, or GFR-1 plus GFR-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.

Key words: IB4; trkA; RET; somatostatin; GFR-1; GFR-2; axotomy; C-fibers; nociception; pain; sprouting; spinal cord

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Copyright © 1998 Society for Neuroscience  0270-6474/98/1883059-14$05.00/0

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