ABSTRACT
Lead (Pb) is an archetypal neurotoxic environmental contaminant because it is pervasive, metabolically nonessential, and toxic through multiple mechanisms. Furthermore, Pb produces sublethal functional impairment at low exposures and is more toxic to the immature than mature brain. In these respects it is similar to other common neurotoxicants, including mercurials, polyaromatic hydrocarbons, and ethanol. Lead’s pervasiveness in the environment is characterized by its presence in all ecological and biological niches of modern Earth (Patterson and Settle, 1993). Though Pb is not a prominent contaminant of the food chain, it is a contaminant of water (from lead pipes and solder), soil (from Pb-containing paint dust and fuel emissions), and dwellings (from Pb-containing paint). Like the other neurotoxicants mentioned, Pb has no known essential role in metabolism. Instead, Pb is thought to exploit metabolic pathways used by other metals and thereby alter normal cell function. That Pb acts by multiple mechanisms at the cellular and molecular levels will be a major theme of this chapter, with emphasis on its affects on astrocytes, which accumulate Pb in the central nervous system (CNS). Other environmental neurotoxicants also act upon numerous targets, and indeed only a few, such as tetrodotoxin, are known to have a single mechanism of action (Lai et al., 2004).
