Lead-Induced Learning Impairment Reversed by Environmental Enrichment

Tomas Guilarte and Christopher Toscano
The Johns Hopkins University Bloomberg School of Public Health
R01ES06189 and T32ES07141

Background: Lead is a potent environmental neurotoxicant with a long history of exposure in children. The developing brain is highly susceptible to lead exposure and long-term deficits in cognitive function are the principal effects of lead exposure in children. Despite significant and effective efforts to reduce lead levels in the environment, 1 in 20 children living in the U.S. have blood lead levels known to produce long-term learning deficits. Chelation therapy is the primary method used to treat lead poisoned children; however, recent studies have shown that while it is effective in reducing blood lead concentrations, it has little impact on reversing the cognitive deficits caused by lead.

It is widely known that a disproportionate number of children at-risk for lead exposure live in low socioeconomic environments. The work of these investigators asked whether an enriched and social environment that stimulates brain function could modify the learning impairments and molecular deficits identified in the brains of lead-exposed laboratory rats.

Advance: The experiments showed that environmental enrichment consisting of housing rats in larger cages with toys, platforms, tunnels and a running wheel reversed the long-term deficits in learning in lead-exposed animals. The investigators also determined two specific molecular events in the brain that may be responsible for the improvement in cognitive function. The lead-exposed rats housed in enrichment cages expressed the induction of a nerve growth factor, brain-derived neurotrophic factor. This nerve growth factor is important for nerve cell survival and synaptic plasticity. Secondly, they found that environmental enrichment reversed the deficits of a component of a key neural cell receptor, N-methyl-D-aspartate receptor subunit 1, in the brains of lead-exposed rats. These molecular changes induced by environmental enrichment were present in the hippocampus, a brain region important in learning and memory and known to be targeted by lead.

Implication: This work demonstrates for the first time that learning impairments in lead-exposed rats can be reversed by environmental enrichment even after the exposure has occurred. The model provides an avenue for further study of molecular events involved in lead neurotoxicity and offers new insights in ameliorating the effects of lead on learning in children.

Citation: Guilarte TR, Toscano CD, McGlothan JL, Weaver SA. Environmental enrichment reverses cognitive and molecular deficits induced by developmental lead exposure. Ann Neurol. 2003 Jan; 53(1):50-6.