The Hopkins study is the first to demonstrate that the long-term deficits in cognitive function caused by lead can be reversed and offers a basis for the treatment of childhood lead intoxication. The findings appear in the online edition of the Annals of Neurology.
"Lead exposure during development causes long-lasting deficits in learning in experimental animals, but our study shows for the first time that these cognitive deficits are reversible," said lead author Tomás R. Guilarte, PhD, professor of environmental health sciences at the Johns Hopkins Bloomberg School of Public Health. "This study is particularly important for two reasons. First, it was not known until now whether the effects of lead on cognitive function were reversible. Secondly, the environmental enrichment that reversed the learning deficits was administered after the animals were exposed to lead. Environmental enrichment could be a promising therapy for treating millions of children suffering from the effects of lead poisoning," added Dr. Guilarte.
For their study, Dr. Guilarte, graduate student Christopher Toscano, research technologist Jennifer McGlothan, and research associate Shelley Weaver observed groups of lead-treated or non-treated (control) rats that were raised in an enriched environment. Enrichment cages were multi-level, containing toys, a running wheel, a hammock, platforms, tunnels, and housed multiple animals. Littermates to these rats were raised in standard-sized laboratory cages that the researchers designated as "isolated environment." To measure the learning ability of rats in the various treatment groups, the researchers trained each rat to find a submerged, invisible platform in a pool of water, called the water maze. Each day of training, they timed how long each rat took to find the platform. They observed that both the lead-exposed and control rats living in the enriched environment learned to find the platform in 20 seconds or less within the four-day training period. The isolated control rats took longer to find the platform, while lead-exposed isolated rats took the longest and nearly 50 percent of them failed to learn the test by the last day of training.
Along with the enhanced learning performance of lead-exposed rats reared in an enriched environment, the researchers found a recovery in the levels of the NR1 subunit of the N-methyl-D-aspartate receptor (NMDAR) in the hippocampus. The NR1 subunit is obligatory for functional NMDAR and these researchers have previously shown that lead targets the NMDAR. The hippocampus is a brain region important for learning and memory. Previous research has determined that the NR1 subunit is essential for learning performance in the water maze.
"We all recognize that children that are intellectually stimulated have a greater capacity to learn. Unfortunately, often times the same children that are exposed to lead, also live in impoverished and neglected homes. It seems, that based on our study, many lead-exposed children would benefit from this type of therapeutic approach," said Dr. Guilarte.
"Environmental Enrichment Reverses Cognitive and Molecular Deficits Induced by Developmental Lead Exposure" was written by Tomás R. Guilarte, PhD, Christopher D. Toscano, MS, Jennifer L. McGlotham, MS, and Shelly A. Weaver, PhD. It is published in the December 2002 edition of the Annals of Neurology.
The research was supported by the National Institute of Environmental Health Sciences.
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