CARBON-DISULFIDE NEUROTOXICITY IN RATS - IV - INCREASED MESSENGER-RNAEXPRESSION OF LOW-AFFINITY NERVE GROWTH-FACTOR RECEPTOR - A SENSITIVEAND EARLY INDICATOR OF PNS DAMAGE

Expression of the low-affinity nerve growth factor receptor (NGF-R) in the peripheral nervous system is regulated by Schwann cell-axonal con tact. Steady-state mRNA levels for NGF-R are very low in the mature pe ripheral nervous system, but are markedly upregulated in sciatic nerve during both primary demyelination (tellurium exposure) and secondary demyelination (Wallerian degeneration). Upregulation also occurs in va rious subdegenerative axonopathy models where there is axonal atrophy, suggesting its usefulness as a marker for subtle perturbations in nor mal axon-Schwann cell interactions (Roberson et al., Mol Brain Res 199 5; 28:231-238). To further test this hypothesis, we examined NGF-R mRN A expression in sciatic nerves of rats exposed to carbon disulfide (CS 2), a toxicant known to cause a distal axonopathy. Adult rats were exp osed to CS2 gas (50, 500, or 800 ppm, 6 hr/day, 5 days/wk) for 2-13 we eks. RNA was isolated from sciatic nerves and levels of mRNA for NGF-R determined by Northern blot analysis. NGF-R mRNA expression increased in a dose-and time-dependent manner. Message levels were already incr eased alter 2 wks of exposure to 800 ppm CS2, and increased further wi th continued exposure. Morphological alterations were not apparent in the sciatic nerve, even at the highest dosage levels with the longest exposure times. Upregulation of NGF-R mRNA is thus an indicator of sub tle alterations in the normal axon-Schwann cell relationship and provi des a sensitive measure of CS2 neurotoxicity. Assay of this marker may also be useful as a rapid and very sensitive general screen for other compounds which are potentially toxic to the peripheral nervous syste m. (C) 1998 Intox Press, Inc.