Ahmadimanesh Mahnaz, Etemad Leila, Morshedi Rad Dorsa, Ghahremani Mohammad Hossein, Mohammadpour Amir Hooshang, Jafarzadeh Esfehani Reza, Jowsey Paul, Behdani Fatemeh, Moallem Seyed Adel, Abbaszadegan Mohammad Reza
Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
Food and Drug Vice Presidency, Mashhad University of Medical Sciences, Mashhad, Iran.
Iran J Basic Med Sci. 2023;26(7):820-829. doi: 10.22038/IJBMS.2023.66496.14595.
This study aimed to evaluate the effect of SSRIs on the expression of miRNAs and their protein targets.
In a 100 day open-label study of citalopram (n=25) and sertraline (n=25), levels of miRNA 16, 132, and 124 and glucocorticoid receptor (GR), Brain-derived neurotrophic factor (BDNF), and serotonin transporter (SERT) protein expression were measured by QRT-PCR and western blot in healthy control (n=20), patients with depression at the baseline, and same patients after 100 days of treatment.
Expression levels of GR and BDNF proteins were lower in the depressed group before treatment as compared with the healthy group (0.0001). The SERT level was higher among the depressed group before treatment in comparison with the healthy group (0.0001). The level of GR and BDNF significantly increased, and SERT expression decreased after receiving sertraline (0.05). When the depressed group received citalopram, only SERT and GR were altered (0.05). Among the microRNAs' expression investigated, mir-124 and mir-132 were higher, and mir-16 was lower among the depressed compared with the healthy group (0.0001). Individuals receiving citalopram only showed an increase in the expression of mir-16 while administration of sertraline led to a significant increase in the expression of mir-16 and a decrease in mir-124 and mir-132 (0.05).
This elucidated the relationship between antidepressant treatment and the expression of different microRNA that control gene expression in various pathways involved in depressed patients. Receiving SSRI can affect the level of these proteins and their relevant microRNAs.
本研究旨在评估选择性5-羟色胺再摄取抑制剂（SSRI）对微小RNA（miRNA）及其蛋白质靶点表达的影响。
在一项为期100天的关于西酞普兰（n = 25）和舍曲林（n = 25）的开放标签研究中，通过定量逆转录聚合酶链反应（QRT-PCR）和蛋白质免疫印迹法，对健康对照组（n = 20）、基线期抑郁症患者以及治疗100天后的同一批患者，检测miRNA 16、132和124以及糖皮质激素受体（GR）、脑源性神经营养因子（BDNF）和5-羟色胺转运体（SERT）的蛋白质表达水平。
与健康组相比，治疗前抑郁症组中GR和BDNF蛋白质的表达水平较低（P<0.0001）。与健康组相比，治疗前抑郁症组中SERT水平较高（P<0.0001）。服用舍曲林后，GR和BDNF水平显著升高，SERT表达降低（P<0.05）。当抑郁症组服用西酞普兰时，只有SERT和GR发生改变（P<0.05）。在所研究的微小RNA表达中，与健康组相比，抑郁症患者中mir-124和mir-132较高，而mir-16较低（P<0.0001）。仅服用西酞普兰的个体mir-16表达增加，而服用舍曲林导致mir-16表达显著增加，mir-124和mir-132表达降低（P<0.05）。
本研究阐明了抗抑郁治疗与不同微小RNA表达之间的关系，这些微小RNA在抑郁症患者涉及的各种途径中控制基因表达。服用SSRI可影响这些蛋白质及其相关微小RNA的水平。
