LSU Neuroscience Center, Louisiana State University Health Sciences Center, New Orleans, LA 70112-2272, USA.
Neurosci Lett. 2011 Jan 3;487(1):94-8. doi: 10.1016/j.neulet.2010.09.079. Epub 2010 Oct 8.
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-кB 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.
已知在某些免疫细胞和脑细胞类型中，老鼠和人脑富集的 microRNA-146a（miRNA-146a）在调节先天免疫反应和炎症信号方面起着重要作用。在这项研究中，我们检测了早、中、晚期阿尔茨海默病（AD）大脑新皮质和海马体中的 miRNA-146a 水平，在几种人类原代脑和视网膜细胞系中，以及在包括 Tg2576、TgCRND8、PSAPP、3xTg-AD 和 5xFAD 在内的 5 种不同的 AD 转基因小鼠模型中。研究发现，在使用白细胞介素 1-β（IL-1β）对原代人神经元-神经胶质（HNG）细胞进行应激的共培养物中，miRNA-146a 的诱导表达显著上调，并且使用特定的 NF-κB 抑制剂（包括姜黄素）抑制了这种上调。miRNA-146a 的表达与 Tg2576 中的老年斑密度和突触病理学以及本研究中使用的 5xFAD 转基因小鼠模型中的突触病理学相关。
