Zhang Y-L, Xing R-Z, Luo X-B, Xu H, Chang R C-C, Zou L-Y, Liu J-J, Yang X-F
Key Laboratory of Modern Toxicology of Shenzhen, Medical Key Laboratory of Guangdong Province, Medical Key Laboratory of Health Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen, China.
Eur Rev Med Pharmacol Sci. 2016 Jul;20(13):2853-62.
MicroRNAs (miRNAs) play an important role in the development of the brain and also implicated in the pathogenesis of neurological diseases such as Alzheimer's disease (AD). Recent studies implied that dysregulation of miRNAs is involved in neuropsychiatric disorders such as anxiety disorder in AD.
In this study, behavioral experiments such as open field test, elevated plus maze test and light-dark box test were performed to evaluate anxiety-like behaviors in a triple transgenic mouse model of AD (3xTg-AD mice), and Q-PCR was used to measure the change of miR-34a expression.
Behavioral tests revealed anxiety-like behaviors in 3xTg-AD mice. Q-PCR assay showed significantly elevated expression of miR-34a in the hippocampus of 3xTg-AD mice compared with the age- and gender-matched wild-type mice. Western-blot analysis showed that the expression of metabotropic glutamate receptor 7 (GRM7) but not fibroblast growth factor-2 (FGF2), two anxiety disorder-related target genes of miR-34a, was significantly decreased in hippocampus of 3xTg-AD mice compared with the wild-type mice.
We concluded that anxiety-like behavior occurred in 3xTg-AD mice with an involvement of miR-34a/GRM7.
微小RNA（miRNA）在大脑发育中起重要作用，并且与诸如阿尔茨海默病（AD）等神经疾病的发病机制有关。最近的研究表明，miRNA失调与AD中的焦虑症等神经精神疾病有关。
在本研究中，进行了旷场试验、高架十字迷宫试验和明暗箱试验等行为实验，以评估AD三重转基因小鼠模型（3xTg-AD小鼠）中的焦虑样行为，并使用定量聚合酶链反应（Q-PCR）来测量miR-34a表达的变化。
行为测试显示3xTg-AD小鼠存在焦虑样行为。Q-PCR分析表明，与年龄和性别匹配的野生型小鼠相比，3xTg-AD小鼠海马中miR-34a的表达显著升高。蛋白质免疫印迹分析显示，与野生型小鼠相比，3xTg-AD小鼠海马中miR-34a的两个与焦虑症相关的靶基因，即代谢型谷氨酸受体7（GRM7）而非成纤维细胞生长因子2（FGF2）的表达显著降低。
我们得出结论，3xTg-AD小鼠出现焦虑样行为，且与miR-34a/GRM7有关。
