Lead induces peripheral nerve segmental demyelination in rats. Arsenic and thallium produce a peripheral neuropathy characterized by axonal degeneration in humans. Mercury and thallium appear to damage both the peripheral and the central nervous system. It is not known whether this difference in effect is due to different molecular forms of the elements, to differential access to various compartments of the nervous system, or to intrinsically different properties of the elements. Using an in vitro model system of dorsal root ganglion neurons and morphometry of neurite outgrowth and myelination, we demonstrated that mercury and arsenic produce 50% inhibition of neurite outgrowth at 3.9 and 9.6 × 10-6 M, respectively, whereas the same degree of inhibition is produced by 1.3 × 10-4 M thallium and 3.3 × 10-4 M lead. Lead also produces complete inhibition of myelination at 1 × 10-6 M, suggesting that a primary effect on myelination is present in this model system as well as in the intact rodent.
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