Cell-Type Specific Responses of the Nervous System to Lead

Cells that make up the nervous system interact in complex, dynamic structural and biochemical contexts to generate organ function. A neurotoxicant that alters the activities of a particular cell type also induces secondary changes in the interactions between this cell and other cells. All types of cell in the nervous system are potential primary or secondary targets for damage by neurotoxic substances. The purpose of this chapter is to examine the reported cell-specific effects of an archetypal environmental neurotoxicant, inorganic lead (Pb), on neurons and neuroglia. Pb is an archetype in the broad sense that, like several environmental neurotoxicants, it affects multiple cell types, employs multiple mechanisms of toxic action, produces sublethal functional impairment to cells at low doses, is widespread in the environment, and is metabolically nonessential. Pb was perhaps the earliest environmental contaminant to be recognized as a neurotoxicant and is the most thoroughly studied to date in vitro. Pb neurotoxicologists have charted their own courses, often guided by progress in neuroscience and cell biology and sometimes pointing out new directions for neurobiology. The approaches that Pb neurotoxicologists have taken or not taken, the roads, paths, and blind alleys, will be discussed in this chapter, in the hope that telling the story will facilitate in vitro studies with other neurotoxicants. This work will be limited to effects of Pb on neurons, astroglia, and myelinating glia (oligodendroglia and Schwann cells), as the effects of Pb on microglia are virtually unstudied.