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 neuropa thy. However, a third of sensory neurons do, not express receptors for the neurotrophins. These neurons are of small diameter and can be ide ntified by the binding of the lectin IB4 and the expression of the enz yme thiamine monophosphatase (TMP). Here we show that these neurons ex press the receptor components for glial-derived neurotrophic factor (G DNF) signaling (RET, GFR alpha-1, and GFR alpha-2). In lumbar dorsal r oot ganglia, virtually all IB4-labeled cells express RET mRNA, and the majority of these cells (79%) also express GFR alpha-1, GFR alpha-2, or GFR alpha-1 plus GFR alpha-2. GDNF, but not nerve growth factor (NG F), can prevent several axotomy-induced changes in these neurons, incl uding the downregulation of IB4 binding, TMP activity, and somatostati n expression. GDNF also prevents the slowing of conduction velocity th at normally occurs after axotomy in a population of small diameter DRG cells and the A-fiber sprouting into lamina II of the dorsal horn. GD NF therefore may be useful in the treatment of peripheral neuropathies and may protect peripheral neurons that are refractory to neurotrophi n treatment.