Environmental enrichment reverses cognitive and molecular deficits induced by developmental lead exposure

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Abstract
Long‐term deficits in cognitive function are the principal effects of lead (Pb2+) exposure in children and can be modeled in experimental animals. Current therapeutic approaches in the treatment of childhood Pb2+ intoxication are not effective in reversing learning deficits once they have occurred. We report that environmental enrichment reverses long‐term deficits in spatial learning produced by developmental Pb2+ exposure in rats. Enhanced learning performance of Pb2+‐exposed animals reared in an enriched environment was associated with recovery of deficits in N‐methyl‐D‐aspartate receptor subunit 1 (NR1) mRNA and induction of brain‐derived neurotrophic factor (BDNF) mRNA in the hippocampus. The effect of environmental enrichment on NR1 and BDNF gene expression was specific to Pb2+‐exposed animals and was present in the absence of changes in the NR2B subunit of the N‐methyl‐D‐aspartate receptor, GluR1, αCamKII, or PSD‐95 gene expression measured in the same animals. Our findings demonstrate that the learning impairments and NR1 subunit mRNA deficits resulting from developmental Pb2+ exposure are reversible if the animals are provided with an enriched environment even after the exposure has occurred. We propose environmental enrichment as a basis for the treatment of childhood Pb2+ intoxication.