Tang Y, Bao J S, Su J H, Huang W
Department of Geriatric, Wuxi No. 2 People's Hospital, Wuxi, Jiangsu, China.
Department of Geriatric, Wuxi No. 2 People's Hospital, Wuxi, Jiangsu, China
Genet Mol Res. 2017 Feb 16;16(1):gmr-16-01-gmr.16019166. doi: 10.4238/gmr16019166.
Alzheimer's disease (AD) is a neurodegenerative disorder, and is the most common type of dementia in the elderly population. Growing evidence indicates that microRNAs (miRNAs) play a crucial role in neuroinflammation associated with AD progression. In this study, we analyzed the expression of microRNA-139 (miR-139) as well as the learning and memory function in AD. We observed that the miR-139 expression was significantly higher in the hippocampus of aged senescence accelerated mouse prone 8 (SAMP8) mice (2.92 ± 0.13) than in the control mice (1.49 ± 0.08). Likewise, the overexpression of miR-139 by means of hippocampal injection impaired the hippocampus-dependent learning and memory formation. In contrast, the downregulation of miR-139 in mice improved learning and memory function in the mice. The level of cannabinoid receptor type 2 (CB2), a potential target gene of miR-139, was inversely correlated with the miR-139 expression in primary hippocampal cells. Furthermore, we demonstrated that miR-139 inversely modulated the responses to proinflammatory stimuli. Together, our findings demonstrate that miR-139 exerts a pathogenic effect in AD by modulating CB2-meditated neuroinflammatory processes.
阿尔茨海默病（AD）是一种神经退行性疾病，也是老年人群中最常见的痴呆类型。越来越多的证据表明，微小RNA（miRNA）在与AD进展相关的神经炎症中起关键作用。在本研究中，我们分析了微小RNA - 139（miR - 139）的表达以及AD中的学习和记忆功能。我们观察到，衰老加速易患8型（SAMP8）老龄小鼠海马中的miR - 139表达（2.92±0.13）显著高于对照小鼠（1.49±0.08）。同样，通过海马注射过表达miR - 139会损害海马依赖性学习和记忆形成。相反，下调小鼠体内的miR - 139可改善小鼠的学习和记忆功能。miR - 139的潜在靶基因大麻素受体2型（CB2）的水平与原代海马细胞中的miR - 139表达呈负相关。此外，我们证明miR - 139可反向调节对促炎刺激的反应。总之，我们的研究结果表明，miR - 139通过调节CB2介导的神经炎症过程在AD中发挥致病作用。
