How Lead Exposure May Work to Damage the Developing Brain

PI: Gary Goldstein
Johns Hopkins University

Background: Elemental lead has been a bane to the existence of man since the beginning of time. Lead has been found in bones as old as 8,500 years. In the twentieth century, tetraethyl lead, used as a "no-knock" additive in automobile fuels, distributed lead to every corner of the world through car exhausts. Although leaded gasoline has been removed from the marketplace, and despite the fact that mean blood lead levels have been decreasing dramatically over the last two decades, lead poisoning remains a major public health problem, especially common in poor urban children. Relatively low-level lead exposure in children can cause permanent deficits in intelligence; however, the biologic mechanism for this effect is unknown.

Advance: Using a rodent model, this team of scientists provides evidence that the effect of lead exposure on a child's brain may be due to reductions in growth and development of the brain's cortex. In rats, individual rodent whiskers are linked to sets of specific cells, known as barrel fields, in the sensory portion of the cortex. Scientists looked at lead-induced damage to the nerve cells that process sensory signals from the rat's whiskers.

Female rats who had just delivered pups were administered lead in their drinking water. The timing of the lead treatment coincided with the development of specific brain structures in the rat pups, who obtained the lead from nursing, and produced blood lead levels in the pups in the range of 1­31 g/dl. These blood lead levels are within the range observed in many inner­city children. Lead exposure caused a decrease in the size of the structures ­the "barrel fields"­ in the rat pups' brains. This finding supports the hypothesis that lead exposure, at levels found in inner-city children, may impair the development of neural cortex and thus cause decreases in intelligence.

Implications: This study demonstrates that a dose-related decrease in the size of specific brain structures is observed in these rats after exposure to relatively low doses of lead during a critical developmental stage. These structural alterations occur in the animals, not at the elevated test doses used in other studies, but at doses equivalent to those actually seen in many poor inner-city children. [Area of Emphasis: Biology of the Nervous System: Development and Disorders; GPRA Goal: Develop new or improved approaches for preventing or delaying the onset or pregression of disease and disability]

Citation: Wilson MA, Johnston MV, Goldstein GW, Blue ME. Neonatal lead exposure impairs development of rodent barrel field cortex. Proc Natl Acad Sci USA 97: 5540-5545, 2000