title: Mechanisms of lead neurotoxicity.
abstract: During the past several years, there has been a renewed interest in the mechanisms by which lead poisoning disrupts brain function. In part, this is related to clinical observations that imply an absence of threshold for toxicity in the immature brain. Many of the neurotoxic effects of lead appear related to the ability of lead to mimic or in some cases inhibit the action of calcium as a regulator of cell function. At a neuronal level, exposure to lead alters the release of neurotransmitter from presynaptic nerve endings. Spontaneous release is enhanced and evoked release is inhibited. The former may be due to activation of protein kinases in the nerve endings and the latter to blockade of voltage-dependent calcium channels. This disruption of neuronal activity may, in turn, alter the developmental processes of synapse formation and result in a less efficient brain with cognitive deficits. Brain homeostatic mechanisms are disrupted by exposure to higher levels of lead. The final pathway appears to be a breakdown in the blood-brain barrier. Again, the ability of lead to mimic or mobilize calcium and activate protein kinases may alter the behavior of endothelial cells in immature brain and disrupt the barrier. In addition to a direct toxic effect upon the endothelial cells, lead may alter indirectly the microvasculature by damaging the astrocytes that provide signals for the maintenance of blood-brain barrier integrity.
authors.affiliation: Kennedy Research Institute, Baltimore, MD 21205.
authors.forename: J P
authors.initials: JP
authors.lastname: Bressler
authors.forename: G W
authors.initials: GW
authors.lastname: Goldstein
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects; D006801:Humans; D007854:Lead / Q000633:toxicity*; D009420:Nervous System / Q000187:drug effects*; D018377:Neurotransmitter Agents / Q000378:metabolism; D011493:Protein Kinase C / Q000502:physiology
chemical_list: D015220:Calcium Channels; D018377:Neurotransmitter Agents; D007854:Lead; D011493:Protein Kinase C; D002118:Calcium