Liu Dandan, Zhao Dandan, Zhao Yingkai, Wang Yan, Zhao Yong, Wen Chengfei
Center of Physical Examination, The First Hospital of Jilin University Changchun, Jilin 130021, China.
Department of Pediatric Gastroenterology, The First Hospital of Jilin University Changchun, Jilin 130021, China.
Curr Alzheimer Res. 2019;16(6):473-482. doi: 10.2174/1567205016666190503145207.
Neuroinflammation has important effects on cognitive functions in the pathophysiological process of Alzheimer's Disease (AD). In the current report, we determined the effects of microRNA-155 (miR-155) on the levels of IL-1β, IL-6 and TNF-α, and their respective receptors in the hippocampus using a rat model of AD.
Real-time RT-PCR, ELISA and western blot analysis were used to examine the miR-155, PICs and PIC receptors. The Morris water maze and spatial working memory tests were used to assess cognitive functions.
miR-155 was increased in the hippocampus of AD rats, accompanied by amplification of IL-1β, IL-6 and TNF-α. Intracerebroventricular infusion of miR-155 inhibitor, but not its scramble attenuated the increases of IL-1β, IL-6 and TNF-α and upregulation of their receptors. MiR-155 inhibitor also attenuated upregulation of apoptotic Caspase-3 in the hippocampus of AD rats. Notably, inhibition of miR- 155 or PIC receptors largely recovered the impaired learning performance in AD rat.
We showed the critical role of miR-155 in regulating the memory impairment in AD rats likely via engagement of neuroinflammatory mechanisms, suggesting that miR-155 and its signaling molecules may present prospects in preventing and/or improving the development of the impaired cognitive functions in AD.
神经炎症在阿尔茨海默病（AD）的病理生理过程中对认知功能具有重要影响。在本报告中，我们使用AD大鼠模型确定了微小RNA-155（miR-155）对海马中白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）及其各自受体水平的影响。
采用实时逆转录聚合酶链反应（RT-PCR）、酶联免疫吸附测定（ELISA）和蛋白质免疫印迹分析来检测miR-155、炎性细胞因子（PICs）及其受体。采用莫里斯水迷宫和空间工作记忆测试来评估认知功能。
AD大鼠海马中的miR-155增加，同时伴有IL-1β、IL-6和TNF-α的扩增。脑室内注入miR-155抑制剂而非其乱序序列可减弱IL-1β、IL-6和TNF-α的增加及其受体的上调。miR-155抑制剂还减弱了AD大鼠海马中凋亡相关半胱天冬酶-3（Caspase-3）的上调。值得注意的是，抑制miR-155或PIC受体可在很大程度上恢复AD大鼠受损的学习能力。
我们表明miR-155在调节AD大鼠记忆损伤中可能通过神经炎症机制发挥关键作用，提示miR-155及其信号分子在预防和/或改善AD患者受损认知功能发展方面可能具有前景。
