Environmental enrichment fails to rescue working memory deficits, neuron loss, and neurogenesis in APP/PS1KI mice
Environmental enrichment fails to rescue working memory deficits, neuron loss, and neurogenesis in APP/PS1KI mice
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DOI：
10.1016/j.neurobiolaging.2010.02.012
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发表时间：
2012-01-01
影响因子：
4.2
通讯作者：
Wirths, Oliver
中科院分区：
文献类型：
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作者：
Cotel, Marie-Caroline;Jawhar, Sadim;Wirths, Oliver
环境富集已被用于各种阿尔茨海默病（AD）的转基因小鼠模型，然而，与矛盾的结果。在这里，我们研究了环境丰富的影响，在一个严重受影响的AD小鼠模型，显示了多种病理改变，包括海马神经元的损失。将APP/PS1 KI和野生型（WT）对照小鼠圈养在标准条件下或配备有各种物体和转轮的富集笼中。评估淀粉样斑块负荷、运动和工作记忆表现、轴突病变以及CA 1神经元数量和海马神经发生。虽然观察到运动性能的部分改善，但4个月的丰富住房在APP/PS1 KI小鼠的工作记忆、A β斑块病理学或神经元损失方面没有显示出有益的效果。此外，海马神经发生没有变化，甚至轴突表型的加重，检测到有过早死亡的趋势。APP/PS1 KI模型代表轻度至重度AD的模型，其显示从2月龄开始的早期行为缺陷，并快速恶化。因此，我们的数据可能表明，体力活动和丰富的环境可能是更有益的轻度认知障碍患者比早期AD患者。(C)2012 Elsevier Inc. All rights reserved.
Environmental enrichment has been used in a variety of transgenic mouse models of Alzheimer's disease (AD), however, with conflicting results. Here we studied the influence of environmental enrichment in a severely affected AD mouse model, showing a multiplicity of pathological alterations including hippocampal neuron loss. APP/PS1KI and wild type (WT) control mice were housed under standard conditions or in enriched cages equipped with various objects and running wheels. Amyloid plaque load, motor and working memory performance, axonopathy, as well as CA1 neuron number and hippocampal neurogenesis were assessed. Although a partial improvement in motor performance was observed, 4 months of enriched housing showed no beneficial effects in terms of working memory, A beta plaque pathology, or neuron loss in APP/PS1KI mice. In addition, no changes in hippocampal neurogenesis and even an aggravation of the axonal phenotype were detected with a tendency toward a premature death. The APP/PS1KI model represents a model for mild to severe AD showing early behavioral deficits starting at 2 months of age with fast deterioration. Therefore our data might suggest that physical activity and enriched environment might be more beneficial in patients with mild cognitive impairment than in patients with incipient AD. (C) 2012 Elsevier Inc. All rights reserved.