Effects of mild chronic cerebral hypoperfusion and early amyloid pathology on spatial learning and the cellular innate immune response in mice
Effects of mild chronic cerebral hypoperfusion and early amyloid pathology on spatial learning and the cellular innate immune response in mice
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DOI：
10.1016/j.neurobiolaging.2012.06.025
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发表时间：
2013-03-01
影响因子：
4.2
通讯作者：
Rivest, Serge
中科院分区：
文献类型：
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作者：
Pimentel-Coelho, Pedro M.;Michaud, Jean-Philippe;Rivest, Serge
了解脑血管因素在阿尔茨海默病（AD）认知能力下降过程中的作用是开发预防治疗的关键一步。在这些因素中，慢性脑灌注不足是阿尔茨海默病发病机制的早期组成部分，可以预测从轻度认知障碍到阿尔茨海默病的进展。在这里，我们研究了轻度慢性脑灌注不足方案对APPswe/PS1转基因AD小鼠模型的影响。我们观察到，右颈总动脉永久性闭塞在年轻的APPswe/PS1小鼠中引起空间学习障碍，而在野生型小鼠中则没有。此外，学习缺陷的程度与皮层β -淀粉样斑块的数量、单核细胞进入血液的动员以及大脑中骨髓源性小胶质细胞的数量密切相关。这些结果表明，在淀粉样蛋白病理的早期阶段，轻微的脑血流量减少可以选择性地诱导认知缺陷，引发细胞先天免疫反应，甚至不会导致神经元死亡。(c) 2013爱思唯尔公司版权所有。
Understanding the contribution of cerebrovascular factors in the progression of cognitive decline in Alzheimer's disease (AD) is a key step for the development of preventive therapies. Among these factors, chronic cerebral hypoperfusion is an early component of AD pathogenesis that can predict the progression from mild cognitive impairment to AD. Here, we investigated the effects of a protocol of mild chronic cerebral hypoperfusion in the APPswe/PS1 transgenic mouse model of AD. We observed that the permanent occlusion of the right common carotid artery induced spatial learning impairments in young APPswe/PS1 mice, but not in their wild type littermates. Furthermore, the extent of learning deficits strongly correlated with the number of cortical beta-amyloid plaques, with the mobilization of monocytes into the blood and with the number of bone marrow-derived microglia in the brain. These results indicate that a mild reduction of cerebral blood flow can selectively induce cognitive deficits at an early stage of amyloid pathology, eliciting a cellular innate immune response, even without causing neuronal death. (c) 2013 Elsevier Inc. All rights reserved.