Background

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.

Methods

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.

Results

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.

Conclusion

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.

中文翻译：

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lncRNA GAS5的下调可通过调节MicroRNA-26a / EGR1轴减轻小鼠抑郁样行为的海马神经元损伤

背景

越来越多的证据证明了几种长的非编码RNA（lncRNA）在抑郁症中的作用。我们旨在检查具有抑郁样行为的小鼠lncRNA生长停滞特异性转录本5（GAS5）的能力及其作用机制。

方法

选择了五十六只健康小鼠用于模型建立。进行莫里斯水迷宫测试和飞人测试以评估学习和记忆能力。通过双荧光素酶报告基因分析证实了lncRNA GAS5与microRNA-26a（miR-26a）之间的结合关系以及miR-26a与EGR1之间的靶标关系。TUNEL染色检测小鼠海马CA1区神经元的凋亡。通过RT检测炎症因子，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）途径和细胞凋亡相关因子的表达。 -qPCR和蛋白质印迹分析。

结果

在具有抑郁样行为的小鼠海马组织中，miR-26a表达下调，而EGR1和lncRNA GAS5表达上调。LncRNA GAS5与miR-26a和miR-26a靶向EGR1特异性结合。lncRNA GAS5沉默抑制了抑郁样行为小鼠炎症因子的释放和海马神经元的凋亡。EGR1抑制PI3K / AKT途径的激活，以促进具有抑郁样行为的小鼠体内炎症因子的释放和海马神经元的凋亡。

结论

我们的研究提供的证据表明，沉默lncRNA GAS5可以通过调节miR-26a / EGR1轴来激活PI3K / AKT通路，从而保护海马神经元免受类似抑郁症行为的小鼠的伤害。