MicroRNA-328a regulates water maze performance in PTZ-kindled rats
MicroRNA-328a regulates water maze performance in PTZ-kindled rats
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MicroRNA-328a 调节 PTZ 点燃大鼠的水迷宫表现
DOI：
10.1016/j.brainresbull.2016.07.008
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发表时间：
2016-07-01
影响因子：
3.8
通讯作者：
Wu, Yuan
中科院分区：
文献类型：
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作者：
Liao, Yuhan;Huang, Yiqing;Wu, Yuan
在我们先前的研究中证实了microRNA-328 a（miR-328 a）在具有记忆障碍的戊四唑（PTZ）点燃大鼠中的下调，而miR-328 a对PTZ点燃大鼠的认知功能障碍的任何贡献仍然未知。本研究探讨了miR-328 a对PTZ点燃大鼠认知功能的影响及其机制。将48只SD雄性大鼠分为以下4组：PTZ点燃组、miR-328 a艾司奥美拉唑组、艾司奥美拉唑对照组和假手术组（每组n = 12）。除假手术组外，其余大鼠均给予PTZ，每次间隔48 h，共14次，建立颞叶癫痫（TLE）模型，并于首次注射PTZ后第2天侧脑室注射miR-328 a希罗米特。采用Morris水迷宫（MWM）测试大鼠的学习记忆能力。RT-qPCR结果显示PTZ组miR-328 a表达下调，经阿司洛尔治疗后miR-328 a表达减少（P < 0.05）。在水迷宫探索实验中，戊四氮组的时间和距离均短于假手术组（P < 0.05），阿托莫西米对照组的时间和距离均长于阿托莫西米组（P < 0.05）。此外，我们发现随着miR-328 a的下调，作为miR-328 a的生物信息学预测靶点的β位点APP裂解酶（BACE）的水平上调。这些发现表明，miR-328 a可能通过调节BACE水平在PTZ点燃大鼠的记忆功能障碍中发挥作用，这将PTZ模型与阿尔茨海默病联系起来。(C)2016年6月，作者。爱思唯尔公司出版
The down-regulation of microRNA-328a (miR-328a) in pentylenetetrazole (PTZ)-kindled rats with memory impairment was demonstrated in our previous study, while any contribution of miR-328a to cognitive dysfunction of PTZ-kindled rats remains unknown. In this study we have investigated the effect and the underlying mechanism of miR-328a on the cognitive function in PTZ-kindled rats. 48 SD male rats were divided into 4 groups as follows: a PTZ kindled group, a miR-328a antagomir group, an antagomir-control group, and a sham group (n = 12 for each). All rats except those from the sham group were treated with PTZ 14 times at intervals of 48 h to establish the temporal lobe epilepsy (TLE) models, and miR-328a antagomir was given to the antagomir group as a treatment by lateral-ventricle injection the day after the first injection of PTZ. Morris water maze (MWM) test was performed to assay their learning and memory abilities. The down-regulation of miR-328a in the PTZ group was confirmed using RT-qPCR and the expression of miR-328a was diminished after antagomir treatment (P < 0.05). In the probe test of water maze, the time and distance of the PTZ group were both shorter than those of the sham group (P < 0.05), and those of the antagomir-control group were both longer than those of the antagomir group (P < 0.05). In addition, we found that with the down-regulation of miR-328a, the levels of Beta-site APP-cleaving enzyme (BACE), which is a bioinformatics-predicted target of miR-328a, were up-regulated. These findings suggest that miR-328a may play a role in memory dysfunction in PTZ-kindled rats by regulating the BACE levels and this links the PTZ model with Alzheimer's disease. (C) 2016 The Authors. Published by Elsevier Inc.