title: Environmental enrichment reverses cognitive and molecular deficits induced by developmental lead exposure.
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, alpha CamKII, 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.
authors.affiliation: Department of Environmental Health Sciences, The Johns Hopkins University, Bloomberg School of Public Health, Baltimore, MD 21205, USA. tguilart@jhsph.edu
authors.forename: Tomás R
authors.initials: TR
authors.lastname: Guilarte
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Toscano
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: McGlothan
authors.forename: Shelley A
authors.initials: SA
authors.lastname: Weaver
mesh_terms: D000367:Age Factors; D000818:Animals; D001835:Body Weight; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics; D003072:Cognition Disorders / Q000503:physiopathology* / Q000628:therapy*; D003213:Conditioning, Psychological / Q000502:physiology; D004195:Disease Models, Animal; D000076122:Disks Large Homolog 4 Protein; D004777:Environment; D005260:Female; D015870:Gene Expression; D006624:Hippocampus / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins; D020263:Lead Poisoning, Nervous System / Q000503:physiopathology* / Q000628:therapy*; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins / Q000235:genetics; D051381:Rats; D020318:Rats, Long-Evans; D018091:Receptors, AMPA / Q000235:genetics; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics; D013028:Space Perception / Q000502:physiology
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D000076122:Disks Large Homolog 4 Protein; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; C501449:Dlg4 protein, rat; C409466:NR1 NMDA receptor; C033652:postsynaptic density proteins