Recent studies indicated a role of microRNAs (miRNAs, small non-coding RNAs which regulate the expression of target genes by acting on mRNAs) in several neural processes, in the pathogenetic mechanisms of neuropsychiatric diseases and in the action of psychotropic drugs. A modulation induced by the antidepressant drug escitalopram on the expression levels of 30 miRNAs was highlighted in the blood of patients suffering from major depressive disorder.

With the aim to investigate the effects of escitalopram in an in vitro model, we performed an analysis of the effects produced by escitalopram on the profiles of the 6 miRNAs found to be more significantly modulated in the above-mentioned study (miR-130b, miR-26a and -26b, let-7f, miR-770-5p, miR-34c-5p) in human U87 glioblastoma cells. Cells were treated with the drug for 24, 48 and 72 h.

The obtained results confirmed a significant increase of let-7f, both after 48 (p = 0.031) and 72 h (p = 0.022), and of miR-26a after 48 h (p = 0.032). On the same experimental model, a transcriptome analysis was conducted after 72 h, highlighting a drug-induced modulation of 1184 protein-coding genes, 207 of which represent let-7f targets. Particularly interesting was the downregulation of BCOR, CCND1 and ATR, validated let-7f targets, which play a key role in the mechanisms of neurogenesis, neuroplasticity and protection from oxidative stress in the brain, indicating that escitalopram could exert downstream effects on gene expression through the regulation of specific miRNAs.

最近的研究表明，microRNA（miRNA，通过作用于mRNA来调节靶基因表达的非编码小RNA）在神经系统疾病，神经精神疾病的发病机制和精神药物的作用中具有重要作用。在患有重度抑郁症的患者的血液中强调了抗抑郁药依西酞普兰对30种miRNA表达水平的调节作用。

为了研究艾司西酞普兰在体外模型中的作用，我们对艾司西酞普兰对在上述研究中发现被更显着调节的6种miRNA的谱图（miR-130b，miR人U87胶质母细胞瘤细胞中的-26a和-26b，let-7f，miR-770-5p，miR-34c-5p）。用该药物处理细胞24、48和72小时。

获得的结果证实，let-7f在48（p = 0.031）和72 h（p = 0.022）之后显着增加，而miR-26a在48 h（p = 0.032）之后都显着增加。在相同的实验模型上，在72小时后进行了转录组分析，突出了药物诱导的1184个蛋白编码基因的调控，其中207个代表let-7f靶标。特别令人感兴趣的是BCOR，CCND1和ATR的下调，验证了let-7f靶标，这些靶标在神经发生，神经可塑性和保护大脑免受氧化应激的机制中起着关键作用，表明依西酞普兰可以通过以下途径对基因表达发挥下游作用：特定miRNA的调控。