Mechanisms of lead neurotoxicity, or looking beyond the lamppost

Despite several decades of research on the neurotoxicology of lead and its continued prominence as a major environmental and occupational health hazard, the mechanisms of its toxic action in the nervous system are still unknown. The differential effects of lead exposure in young children and adults, as well as inconsistencies between in vivo and in vitro studies, suggest that lead toxicity may have multiple mechanisms in the central nervous system (CNS). Two are: neurodevelopmental toxicity, possibly involving interference with cell adhesion molecules, resulting in miswiring of the CNS during early development and possibly permanent dysfunction; and neuropharma-cological toxicity, which might involve interactions between lead and calcium and lead and zinc, resulting in interference with neurotransmission at the synapse. This may be reversible.