Increased expression of miRNA-146a in Alzheimer's disease transgenic mouse models.
Increased expression of miRNA-146a in Alzheimer's disease transgenic mouse models.
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DOI：
10.1016/j.neulet.2010.09.079
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发表时间：
2011-01-03
影响因子：
2.5
通讯作者：
Lukiw WJ
中科院分区：
文献类型：
--
作者：
Li YY;Cui JG;Hill JM;Bhattacharjee S;Zhao Y;Lukiw WJ
已知小鼠和人脑富集的micro-RNA-146 a（miRNA-146 a）在调节某些免疫细胞和脑细胞类型中的先天免疫应答和炎症信号传导中是重要的。在这项研究中，我们检测了早期，中期和晚期阿尔茨海默病（AD）新皮层和海马，几种人类原代脑和视网膜细胞系以及5种不同的AD转基因小鼠模型（包括Tg 2576，TgCRND 8，PSAPP，3xTg-AD和5xFAD）中的miRNA-146 a水平。发现在使用白细胞介素1-β（IL-1β）应激的人神经胶质（HNG）细胞的原代共培养物中，miRNA-146 a的诱导性表达显著上调，并且使用包括姜黄素在内的特异性NF-κB抑制剂淬灭这种上调。miRNA-146 a的表达与Tg 2576和5xFAD转基因小鼠模型中的老年斑密度和突触病理学相关，这些小鼠模型用于研究这种常见的神经退行性疾病。
A mouse and human brain-enriched micro-RNA-146a (miRNA-146a) is known to be important in modulating the innate immune response and inflammatory signaling in certain immunological and brain cell types. In this study we examined miRNA-146a levels in early-, moderate- and late-stage Alzheimer’s disease (AD) neocortex and hippocampus, in several human primary brain and retinal cell lines, and in 5 different transgenic mouse models of AD including Tg2576, TgCRND8, PSAPP, 3xTg-AD and 5xFAD. Inducible expression of miRNA-146a was found to be significantly up-regulated in a primary co-culture of human neuronal–glial (HNG) cells stressed using interleukin1-beta (IL-1β), and this up-regulation was quenched using specific NF-κB inhibitors including curcumin. Expression of miRNA-146a correlated with senile plaque density and synaptic pathology in Tg2576 and in 5xFAD transgenic mouse models used in the study of this common neurodegenerative disorder.