NGFR-MESSENGER-RNA EXPRESSION IN SCIATIC-NERVE - A SENSITIVE INDICATOR OF EARLY STAGES OF AXONOPATHY

Expression of the low-affinity nerve growth factor receptor (NGFR) in the sciatic nerve (particularly Schwann cells) is high during developm ent but is downregulated upon establishment of the mature axon-Schwann cell relationship. NGFR is re-expressed by Schwann cells if this rela tionship is altered by degeneration of axons (axotomy) or myelin (tell urium intoxication). To determine the sensitivity of NGFR expression t o axonal injury, we have assayed NGFR-mRNA levels in proximal and dist al regions of nerves exposed to the axonopathic agents acrylamide and isoniazid, as well as in proximal and distal stumps of axotomized nerv es. NGFR-mRNA was elevated in all three models and correlated regional ly with sites of axonal perturbation. Tn distal regions of acrylamide- and isoniazid-intoxicated nerves, NGFR-mRNA was elevated at least 2 d ays prior to visible signs of axonal degeneration as assayed by morpho logical techniques utilizing light microscopy. NGFR-mRNA was also elev ated in proximal regions of axotomized and acrylamide-intoxicated nerv es prior to signs of axonal degeneration. In these models, increased m RNA expression correlated with alterations in the size distribution of axonal cross sections. The common response in all of these situations indicates that NGFR expression, in addition to being a marker for axo nal degeneration, is also a sensitive indicator of less profound pertu rbations in normal axon-Schwann cell interactions, including early sta ges of axonopathy. We suggest that assay for NGFR-mRNA may be utilized as a rapid and simple method (relative to more labor-intensive morpho logical methods) to screen for peripheral neurotoxicity. Additionally, regional analysis (distal versus proximal) may give insight into the sequence of events involved in the neuropathology of such disorders.