title: CSF miR-16 is decreased in major depression patients and its neutralization in rats induces depression-like behaviors via a serotonin transmitter system.
abstract: 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 ELISA 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.
  
  
  CONCLUSIONS
  We did not detect SERT protein in human brain due to the impossibility of sample collection.
  
  
  CONCLUSIONS
  Our study suggested that CSF miR-16 participated in the physiopathology of MDD via the modulation of serotonin transmitter system in brain.
authors.affiliation: Molecular Biology Laboratory, Hangzhou Seventh People's Hospital, 305 Tianmushan Road, Hangzhou 310013, Zhejiang, China.
authors.forename: Ming-Fen
authors.initials: MF
authors.lastname: Song
authors.affiliation: Department of Psychiatry, Hangzhou Seventh People's Hospital, 305 Tianmushan Road, Hangzhou 310013, Zhejiang, China.
authors.forename: Jie-Zheng
authors.initials: JZ
authors.lastname: Dong
authors.affiliation: Department of Pharmacy, Hangzhou Seventh People's Hospital, 305 Tianmushan Road, Hangzhou 310013, Zhejiang, China.
authors.forename: Yu-Wen
authors.initials: YW
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, Hangzhou Seventh People's Hospital, 305 Tianmushan Road, Hangzhou 310013, Zhejiang, China.
authors.forename: Jun
authors.initials: J
authors.lastname: He
authors.affiliation: Department of Psychiatry, Hangzhou Seventh People's Hospital, 305 Tianmushan Road, Hangzhou 310013, Zhejiang, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Ju
authors.affiliation: Molecular Biology Laboratory, Hangzhou Seventh People's Hospital, 305 Tianmushan Road, Hangzhou 310013, Zhejiang, China.
authors.forename: Long
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Psychiatry, Hangzhou Seventh People's Hospital, 305 Tianmushan Road, Hangzhou 310013, Zhejiang, China.
authors.forename: Yong-Hua
authors.initials: YH
authors.lastname: Zhang
authors.affiliation: Department of Psychiatry, Hangzhou Seventh People's Hospital, 305 Tianmushan Road, Hangzhou 310013, Zhejiang, China.
authors.forename: Jian-Fei
authors.initials: JF
authors.lastname: Shi
authors.affiliation: Department of Human Resources, Hangzhou Seventh People's Hospital, 305 Tianmushan Road, Hangzhou 310013, Zhejiang, China. Electronic address: hzs7lwfb@163.com.
authors.forename: Ya-Ying
authors.initials: YY
authors.lastname: Lv
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D000070416:Antagomirs; D001522:Behavior, Animal / Q000187:drug effects; D016022:Case-Control Studies; D003863:Depression / Q000097:blood / Q000134:cerebrospinal fluid / Q000235:genetics* / Q000523:psychology*; D003865:Major Depressive Disorder / Q000097:blood / Q000134:cerebrospinal fluid / Q000235:genetics* / Q000523:psychology*; D005260:Female; D006801:Humans; D007276:Injections, Intraventricular; D008297:Male; D035683:MicroRNAs / Q000037:antagonists & inhibitors* / Q000097:blood / Q000134:cerebrospinal fluid*; D008875:Middle Aged; D009841:Oligonucleotides / Q000008:administration & dosage / Q000494:pharmacology; D011903:Raphe Nuclei / Q000378:metabolism; D051381:Rats; D012701:Serotonin / Q000134:cerebrospinal fluid / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects; D055815:Young Adult
chemical_list: D000070416:Antagomirs; C505362:MIRN16 microRNA, human; D035683:MicroRNAs; D009841:Oligonucleotides; D050486:Serotonin Plasma Membrane Transport Proteins; C000601969:antagomir-16; D012701:Serotonin
keywords: Cerebrospinal fluid; Hamilton score; Major depressive disorder; Serotonin; Serotonin transporter; miR-16