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

Cell Cycle. 2018;17(24):2745-2755. doi: 10.1080/15384101.2018.1556060. Epub 2018 Dec 27.

Abstract

Objective: The aim of this study was to investigate the mechanism of miR-221 in depression.

Methods: The molecules expressions were measured by qRT-PCR and western blot. The sucrose preference test (SPT), forced swimming test (FST) and tail suspension test (TST) were used to detect depressive-like symptoms. MTT assay and flow cytometric was used to measure the proliferation and apoptosis of hippocampal neuronal.

Results: MiR-221 expression in the cerebrospinal fluid and serum of major depressive disorder patients and the hippocampus of chronic unpredictable mild stress (CUMS) mice were increased, while the expression of Wnt2, p-CREB and BDNF were decreased. 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 targeted regulate Wnt2, and knockdown of Wnt2 reversed the effect of miR-221 inhibitor on the proliferation and apoptosis of hippocampal neurons and countered the promoting effect of miR-221 inhibitor 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: Major depressive disorder; Wnt2/CREB/BDNF; miR-221.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Antagomirs / metabolism
  • Apoptosis
  • Brain-Derived Neurotrophic Factor / metabolism*
  • CREB-Binding Protein / metabolism*
  • Case-Control Studies
  • Depressive Disorder, Major / genetics
  • Depressive Disorder, Major / pathology*
  • Female
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / analysis
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neurons / cytology
  • Neurons / metabolism*
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Stress, Physiological
  • Wnt2 Protein / antagonists & inhibitors
  • Wnt2 Protein / genetics
  • Wnt2 Protein / metabolism*

Substances

  • Antagomirs
  • Brain-Derived Neurotrophic Factor
  • MIRN221 microRNA, mouse
  • MicroRNAs
  • RNA, Small Interfering
  • Wnt2 Protein
  • CREB-Binding Protein

Grants and funding

This research was supported by the National Natural Science Foundation of China (No.81571318 to XS; No.81401110 to XL), Health and Family Planning Commission of Henan Province (No.201501015 to XS), Department of Science and Technology of Henan Province (No. 162102410061 to XS; No.2017JQ023 to XS), School and Hospital Co-Incubation Funds (No.2017-BSTDJJ-04 to XS).