Environmental enrichment reverses cognitive and molecular deficits induced by developmental lead exposure
Environmental enrichment reverses cognitive and molecular deficits induced by developmental lead exposure
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DOI：
10.1002/ana.10399
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发表时间：
2003-01-01
影响因子：
11.2
通讯作者：
Weaver, SA
中科院分区：
文献类型：
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作者：
Guilarte, TR;Toscano, CD;Weaver, SA
长期的认知功能缺陷是铅(Pb2+)暴露对儿童的主要影响，可以在实验动物中建立模型。目前治疗慢性P‘中毒的方法一旦发生，在逆转学习障碍方面并不是有效的。我们报道，环境的丰富逆转了由于发育中的Pb2+暴露而导致的大鼠空间学习的长期缺陷。在丰富的环境中饲养的铅暴露动物的学习成绩增强与N-甲基-D-天冬氨酸受体亚单位1(NR1)mRNA的恢复和海马区脑源性神经营养因子(BDNF)mRNA的诱导有关。环境丰富对NR1和BDNF基因表达的影响仅限于Pb2+暴露动物，在同一动物中测量到的N-甲基-D-天冬氨酸受体NR2B亚单位GluR1、αCamKII或PSD-95基因表达没有变化。我们的研究结果表明，即使在PH2+暴露发生后，如果给动物提供丰富的环境，由发育性PH2+暴露引起的学习障碍和NR1亚单位mRNA缺失是可逆的。我们建议将环境浓缩作为治疗儿童Pb2+中毒的基础。
Long-term deficits in cognitive function are the principal effects of lead (Pb2+) exposure in Children and can be modeled in experimental animals. Current therapeu ic approaches in the eat e t of c ood P _' 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, alphaCamKII, 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 Ph2+ 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.