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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Behav. Neurosci. | doi: 10.3389/fnbeh.2018.00059

MiR-221 is involved in depression by regulating Wnt2/CREB/BDNF axis in hippocampal neurons

Nan Lian1, Hailong Lv2, Wenbing Guo2, Yidong Shen2, Renlong Wu2, Yong Liu2, Furong Zhu2, Maorong Hu2, Jianjun Ou2 and  Jingping Zhao2, 3*
  • 1First Affiliated Hospital of Zhengzhou University, China
  • 2Second Xiangya Hospital, Central South University, China
  • 3Education Department of Hunan Province, China

Objective The aim of this study was to investigate the mechanism of miR-221 in depression.
Method First, the expressions of 6 miRNAs in cerebrospinal fluid (CSF) and serum of major depressive disorder (MDD) patients were detected by qRT-PCR. Then, the expressions of miR-221, Wnt2, p-CREB (cAMP-response element binding protein) and brain-derived neurotrophic factor (BDNF) in chronic unpredictable mild stress (CUMS) mice were measured by qRT-PCR and western blot, respectively. The sucrose preference test (SPT), forced swimming test (FST) and tail suspension test (TST) were used to detect depressive-like symptoms. MTT assay was used to measure hippocampal neuronal proliferation. Flow cytometric was used to detect neuronal apoptosis. The relationship between miR-221 and Wnt2 was analyzed by Dual-luciferase reporter assays.
Result The results showed that miR-221 levels in the CSF and serum of MDD patients and the hippocampus of CUMS mice were abnormally increased. Meanwhile, the expression of Wnt2, p-CREB and BDNF were decreased in the hippocampus of CUMS mice. Additionally, silence of miR-221 increased sucrose preference of CUMS mice and shortened the immobility time of CUMS mice in SPT and FST. MiR-221 could regulate the expression of Wnt2, p-CREB and BDNF. Moreover, software predicted a potential binding site between miR-221 and Wnt2. Knockdown of Wnt2 could reverse the effect of silence miR-221 on the proliferation and apoptosis of hippocampal neurons and counter the promoting effect of silence miR-221 on the expression of Wnt2, p-CREB and BDNF.
Conclusion MiR-221 could promote the development of depression by regulating Wnt2/CREB/BDNF axis.

Keywords: MDD, miR-221, Wnt2/CREB/BDNF, Cerebrospinal Fluid, Neuronal apoptosis

Received: 14 Nov 2017; Accepted: 13 Mar 2018.

Edited by:

Mikhail Lebedev, Duke University, United States

Reviewed by:

Paul B. Fisher, Virginia Commonwealth University, United States
Sandeep Sharma, CRCHUM & MDRC, Canada
Pei Jiang, Jining Medical University, China  

Copyright: © 2018 Lian, Lv, Guo, Shen, Wu, Liu, Zhu, Hu, Ou and Zhao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Jingping Zhao, Second Xiangya Hospital, Central South University, Changsha, China,