Folic acid deficiency enhances abeta accumulation in APP/PS1 mice brain and decreases amyloid-associated miRNAs expression
Folic acid deficiency enhances abeta accumulation in APP/PS1 mice brain and decreases amyloid-associated miRNAs expression
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叶酸缺乏会增强 APP/PS1 小鼠大脑中 abeta 的积累并降低淀粉样蛋白相关 miRNA 的表达
DOI：
10.1016/j.jnutbio.2015.07.020
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发表时间：
2015-12-01
影响因子：
5.6
通讯作者：
Huang, Guowei
中科院分区：
文献类型：
--
作者：
Liu, Huan;Tian, Tian;Huang, Guowei
最近的研究工作揭示了微小RNA（microRNA，miRNA）通路在阿尔茨海默病（Alzheimer's disease，AD）发病机制中的作用。流行病学研究已经揭示了叶酸缺乏和AD风险之间的关联。然而，叶酸缺乏对AD动物中miRNA表达的影响尚未观察到。我们的目的是发现叶酸缺乏是否会增强淀粉样蛋白β（A β）。在APP/PS1小鼠中，肽沉积和调节淀粉样蛋白相关miRNA及其靶基因的表达。APP/PS1小鼠和N2 a细胞用叶酸缺乏的饮食或培养基处理。采用Morris水迷宫评价小鼠的认知功能。聚合酶链反应（PCR）芯片检测miRNA谱。通过实时定量PCR验证不同表达的miRNAs。A β斑块的沉积通过免疫组织化学和酶联免疫吸附试验进行评价。Western blot法检测小鼠脑和N2 a细胞APP和BACE 1蛋白表达。叶酸缺乏可加重AD小鼠的淀粉样病变。AD+FD组在探针测试期间在靶区花费的时间较短。对预测靶向这些基因的miRNA的分析揭示了几种受叶酸缺乏差异调节的miRNA候选物。在叶酸缺乏处理的APP/PS1小鼠脑和N2 a细胞中，miR-106 a-5 p、miR-200 b-3 p和miR-339- 5 p表达下调，而其靶基因APP和BACE 1表达上调。总之，叶酸缺乏可增强APP/PS1小鼠脑中A β的积累，并降低淀粉样蛋白相关miRNA的表达。2015 Elsevier Inc. All rights reserved.
Recent efforts have revealed the microRNA (miRNA) pathways in the pathogenesis of Alzheimer's disease (AD). Epidemiological studies have revealed an association between folic acid deficiency and AD risk. However, the effects of folic acid deficiency on miRNA expression in AD animals have not been observed. We aimed to find if folic acid deficiency may enhance amyloid-beta (A beta.) peptide deposition and regulate amyloid-associated miRNAs and their target genes expression in APP/PS1 mice. APP/PS1 mice and N2a cells were treated with folic acid-deficient diet or medium. Cognitive function of mice was assessed using the Morris water maze. miRNA profile was tested by polymerase chain reaction (PCR) array. Different expressional miRNAs were validated by real-time PCR. The deposition of A beta plaques was evaluated by immunohistochemistry and enzyme-linked immunosorbent assay. APP and BACE1 proteins in mice brain and N2a cells were determined by Western blot. Folic acid deficiency aggravated amyloid pathology in AD mice. The AD+FD group showed shorter time spent in the target zone during the probe test. Analysis of miRNAs predicted to target these genes revealed several miRNA candidates that were differentially modulated by folic acid deficiency. In APP/PS1 mice brains and N2a cells with folic acid-deficient treatment, miR-106a-5p, miR-200b-3p and miR-339-5p were down-regulated, and their target genes APP and BACE1 were up-regulated. In conclusion, folic acid deficiency can enhance A beta accumulation in APP/PS1 mice brain and decrease amyloid-associated miRNAs expression. 2015 Elsevier Inc. All rights reserved.