Critical Processes in CNS Development and the Pathogenesis of Early Injuries

Abstract

Though mercury and lead exposure are known to be more injurious to developing CNS than mature CNS, the nature of the difference is not understood. If the only difference is in accumulation or retention of the toxic agents, then it should be possible to apply the same tests of toxicity, no matter when exposure occurs. On the other hand, if developing tissue responds to metals in ways that mature tissue does not, then the nature of the injury may be different in subjects exposed at different times. In this case, the measures best suited to detect adult toxicity might be inappropriate to detect toxicity after early exposure. One way to evaluate whether metals interfere with development is to test the integrity of processes which occur only in developing CNS. There is already some evidence that mercury and/or lead alter several such processes. Neuron proliferation, formation of glia and myelin, cell migration, development of connections, and differentiation of transmitter characteristics all have been reported to be affected by early exposure to metals. Interruption of these developmental events by other teratogens has been shown to cause permanent alterations in nervous system form and function. The experimental paradigms necessary to demonstrate failures in developmental processes are not necessarily the same as those used in general toxicity testing. Therefore, it would be useful to apply more varied experimental approaches to the questions surrounding metal effects on developing nervous system.