Enrichment improves cognition in AD mice by amyloid-related and unrelated mechanisms
Enrichment improves cognition in AD mice by amyloid-related and unrelated mechanisms
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DOI：
10.1016/j.neurobiolaging.2006.04.009
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发表时间：
2007-06-01
影响因子：
4.2
通讯作者：
Potter, Huntington
中科院分区：
文献类型：
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作者：
Costa, David A.;Craechiolo, Jennifer R.;Potter, Huntington
终身认知刺激与阿尔茨海默病（AD）的风险降低有关，但因果关系难以证明。因此，我们试图研究环境富集（EE）的预防潜力，使用表达人类突变早老素-1和淀粉样前体蛋白（PS1/PDAPP）的小鼠。断奶时，将小鼠置于富集或标准饲养环境中。4.5-6个月时的行为测试表明，环境富集的PS1/PDAPP小鼠的表现优于标准饲养中的小鼠，并且在多个认知领域与非转基因小鼠在行为上难以区分。PS1/PDAPP小鼠暴露于环境富集和行为测试，但不单独暴露于EE，显示脑β-淀粉样蛋白减少50%，而树突形态没有改善。微阵列分析显示，大的富集诱导的海马表达的基因/蛋白质相关的A β螯合和突触可塑性的变化。这些结果表明，EE通过双重机制，包括淀粉样蛋白依赖性和非依赖性机制，保护AD转基因小鼠免受认知障碍。(c)2006年爱思唯尔公司All rights reserved.
Lifelong cognitive stimulation is associated with a lower risk of Alzheimer's disease (AD), but causality is difficult to prove. We therefore sought to investigate the preventative potential of environmental enrichment (EE) using mice expressing both human mutant presenilin-1 and the amyloid precursor protein (PS1/PDAPP). At weaning, mice were placed into either an enriched or standard housing environment. Behavioral testing at 4.5-6 months showed that environmentally enriched PS1/PDAPP mice outperformed mice in standard housing, and were behaviorally indistinguishable from non-transgenic mice across multiple cognitive domains. PS1/PDAPP mice exposed to both environmental enrichment and behavioral testing, but not to EE alone, showed 50% less brain beta-amyloid without improved dendritic morphology. Microarray analysis revealed large enrichment-induced changes in hippocampal expression of genes/proteins related to A beta sequestration and synaptic plasticity. These results indicate that EE protects against cognitive impairment in AD transgenic mice through a dual mechanism, including both amyloid dependent and independent mechanisms. (c) 2006 Elsevier Inc. All rights reserved.