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Molecular and cellular neurosciences v.85, 2017년, pp.220 - 225   SCI SCIE
본 등재정보는 저널의 등재정보를 참고하여 보여주는 베타서비스로 정확한 논문의 등재여부는 등재기관에 확인하시기 바랍니다.

Study of the in vitro modulation exerted by the antidepressant drug escitalopram on the expression of candidate microRNAs and their target genes

Maffioletti, Elisabetta (Faculty of Psychology, eCampus University, Novedrate, Como, Italy ) ; Salvi, Alessandro (Dept of Molecular and Translational Medicine, Div of Biology and Genetics, Univ of Brescia, Italy ) ; Conde, Isabel (Dept of Molecular and Translational Medicine, Div of Biology and Genetics, Univ of Brescia, Italy ) ; Maj, Carlo (Genetics Unit, IRCCS Centro S. Giovanni di Dio, Fatebenefratelli, Brescia, Italy ) ; Gennarelli, Massimo (Genetics Unit, IRCCS Centro S. Giovanni di Dio, Fatebenefratelli, Brescia, Italy ) ; De Petro, Giuseppina (Dept of Molecular and Translational Medicine, Div of Biology and Genetics, Univ of Brescia, Italy ) ; Bocchio-Chiavetto, Luisella (Faculty of Psychology, eCampus University, Novedrate, Como, Italy ) ;
  • 초록  

    Abstract 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 72h. The obtained results confirmed a significant increase of let-7f, both after 48 (p=0.031) and 72h (p=0.022), and of miR-26a after 48h (p=0.032). On the same experimental model, a transcriptome analysis was conducted after 72h, 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. Highlights Escitalopram enhances let-7f and miR-26a (microRNAs) levels in cultured neural cells. BCOR, CCND1 and ATR (validated targets of let-7f) are downregulated by escitalopram.


  • 주제어

    Cell culture .   Escitalopram .   Antidepressant drugs .   microRNAs .   Transcriptome .   Gene expression.  

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