Department of Medical Psychology, The First Affiliated Hospital of Wannan Medical College, No. 2, Zheshan West Road, Wuhu 241001, Anhui, PR China.
Department of Clinical Medical Psychology, The Second People's Hospital of Wuhu, Wuhu 241001, Anhui, PR China.
J Stroke Cerebrovasc Dis. 2021 Mar;30(3):105550. doi: 10.1016/j.jstrokecerebrovasdis.2020.105550. Epub 2020 Dec 18.
Accumulating evidences have demonstrated the roles of several long non-coding RNAs (lncRNAs) in depression. We aim to examine the capabilities of lncRNA growth arrest-specific transcript 5 (GAS5) on mice with depression-like behaviors and the mechanism of action.
Fifty-six healthy mice were selected for model establishment. Morris water maze test and trapeze test were performed for evaluating learning and memory ability. The binding relationship between lncRNA GAS5 and microRNA-26a (miR-26a) and the target relationship between miR-26a and EGR1 were verified by dual-luciferase reporter gene assay. The apoptosis of neurons in the hippocampal CA1 region of mice was detected by TUNEL staining. The expression of inflammatory factors, lncRNA GAS5, miR-26a, early growth response gene 1 (EGR1), phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway- and apoptosis-related factors in hippocampal tissues was tested by RT-qPCR and western blot analysis.
miR-26a expression was down-regulated while EGR1 and lncRNA GAS5 expression were up-regulated in hippocampal tissues of mice with depression-like behaviors. LncRNA GAS5 specifically bound to miR-26a and miR-26a targeted EGR1. Silencing of lncRNA GAS5 curtailed the release of inflammatory factors and the apoptosis of hippocampal neuron of mice with depression-like behaviors. EGR1 suppressed PI3K/AKT pathway activation to promote the release of inflammatory factors and the apoptosis of hippocampal neurons in mice with depression-like behaviors.
Our study provides evidence that silencing of lncRNA GAS5 could activate PI3K/AKT pathway to protect hippocampal neurons against damage in mice with depression-like behaviors by regulating the miR-26a/EGR1 axis.
越来越多的证据表明，几种长链非编码 RNA（lncRNA）在抑郁症中发挥作用。我们旨在研究 lncRNA 生长停滞特异性转录物 5（GAS5）对具有抑郁样行为的小鼠的作用能力及其作用机制。
选择 56 只健康小鼠建立模型。通过 Morris 水迷宫试验和秋千试验评估学习和记忆能力。通过双荧光素酶报告基因试验验证 lncRNA GAS5 与 microRNA-26a（miR-26a）的结合关系以及 miR-26a 与 EGR1 的靶关系。通过 TUNEL 染色检测小鼠海马 CA1 区神经元的凋亡情况。通过 RT-qPCR 和 Western blot 分析检测海马组织中炎症因子、lncRNA GAS5、miR-26a、早期生长反应基因 1（EGR1）、磷酸肌醇 3-激酶（PI3K）/蛋白激酶 B（AKT）通路和凋亡相关因子的表达。
抑郁样行为小鼠海马组织中 miR-26a 表达下调，EGR1 和 lncRNA GAS5 表达上调。lncRNA GAS5 特异性结合 miR-26a，miR-26a 靶向 EGR1。沉默 lncRNA GAS5 可减少抑郁样行为小鼠海马组织中炎症因子的释放和海马神经元的凋亡。EGR1 抑制 PI3K/AKT 通路的激活，促进抑郁样行为小鼠海马神经元中炎症因子的释放和凋亡。
本研究表明，沉默 lncRNA GAS5 可通过调节 miR-26a/EGR1 轴激活 PI3K/AKT 通路，保护抑郁样行为小鼠海马神经元免受损伤。
