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

Authors

  • Tomás R. Guilarte PhD,

    Corresponding author
    1. Department of Environmental Health Sciences, The Johns Hopkins University, Bloomberg School of Public Health, Baltimore, MD
    • Department of Environmental Health Sciences, The Johns Hopkins University, Bloomberg School of Public Health, 615 North Wolfe Street, Room W2001, Baltimore, MD 21205
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  • Christopher D. Toscano MS,

    1. Department of Environmental Health Sciences, The Johns Hopkins University, Bloomberg School of Public Health, Baltimore, MD
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  • Jennifer L. McGlothan MS,

    1. Department of Environmental Health Sciences, The Johns Hopkins University, Bloomberg School of Public Health, Baltimore, MD
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  • Shelley A. Weaver PhD

    1. Department of Environmental Health Sciences, The Johns Hopkins University, Bloomberg School of Public Health, Baltimore, MD
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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.

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