CSF miR-16 is decreased in major depression patients and its neutralization in rats induces depression-like behaviors via a serotonin transmitter system

JOURNAL OF AFFECTIVE DISORDERS

卷:178

Article

Song, Ming-Fen¹  Dong, Jie-Zheng²  Wang, Yu-Wen³  He, Jun³  Ju, Xuan²  Zhang, Long¹  Zhang, Yong-Hua²  Shi, Jian-Fei²  Lv, Ya-Ying⁴ 

[1] Hangzhou Seventh Peoples Hosp, Mol Biol Lab, Hangzhou 310013, Zhejiang, Peoples R China

[2] Hangzhou Seventh Peoples Hosp, Dept Psychiat, Hangzhou 310013, Zhejiang, Peoples R China

[3] Hangzhou Seventh Peoples Hosp, Dept Pharm, Hangzhou 310013, Zhejiang, Peoples R China

[4] Hangzhou Seventh Peoples Hosp, Dept Human Resources, Hangzhou 310013, Zhejiang, Peoples R China

关键词: Major depressive disorder;    miR-16;    Serotonin;    Hamilton score;    Cerebrospinal fluid;    Serotonin transporter;   

DOI  :  10.1016/j.jad.2015.02.022

来源: Elsevier

【 摘 要 】

Background: Animal and cell line studies demonstrated that miR-16 may be associated with major depressive disorder (MDD) via regulation of the expression of serotonin transporter (SERT) gene. However, human studies about miR-16 of patients with MDD are still lacking. The aim of this study was to investigate the possible involvement of miR-16 in the mechanism of MDD in humans. Methods: Thirty-six drug-free patients with MDD and 30 healthy controls aged between 18 and 45 years old were recruited. 24-item Hamilton depression scale test was performed for each subject. MiR-16 in cerebrospinal fluid (CSF) and blood, as well as serotonin in CSF were assayed by the qRT-PCR or ELBA method. To confirm the role of CSF miR-16 in MDD, animal study about intracerebroventricular injection of anti-miR-16 was also performed. Depression-like behaviors, CSF miR-16 and serotonin, blood miR-16, and raphe SERT protein of rats were also tested. Results: CSF miR-16 in MDD patients was significantly lower than that in controls. It was negatively correlated with Hamilton scores and positively associated with CSF serotonin. However, blood miR-16 was not significantly different between two groups and it was not statistically correlated with CSF miR-16. In animal study, anti-miR-16-treated rats were evaluated to exhibit depression-like behaviors, extremely lower CSF miR-16, significantly higher CSF serotonin, and obviously higher raphe SERT protein than control rats. Limitation: We did not detect SERT protein in human brain due to the impossibility of sample collection. Conclusion: Our study suggested that CSF miR-16 participated in the physiopathology of MDD via the modulation of serotonin transmitter system in brain. (C) 2015 Elsevier B.V. All rights reserved.

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