MiR-218: a molecular switch and potential biomarker of susceptibility to stress

Mol Psychiatry. 2020 May;25(5):951-964. doi: 10.1038/s41380-019-0421-5. Epub 2019 Apr 12.


Low miR-218 expression in the medial prefrontal cortex (mPFC) is a consistent trait of depression. Here we assessed whether miR-218 in the mPFC confers resilience or susceptibility to depression-like behaviors in adult mice, using the chronic social defeat stress (CSDS) model of depression. We also investigated whether stress-induced variations of miR-218 expression in the mPFC can be detected in blood. We find that downregulation of miR-218 in the mPFC increases susceptibility to a single session of social defeat, whereas overexpression of miR-218 selectively in mPFC pyramidal neurons promotes resilience to CSDS and prevents stress-induced morphological alterations to those neurons. After CSDS, susceptible mice have low levels of miR-218 in blood, as compared with control or resilient groups. We show further that upregulation and downregulation of miR-218 levels specifically in the mPFC correlate with miR-218 expression in blood. Our results suggest that miR-218 in the adult mPFC might function as a molecular switch that determines susceptibility vs. resilience to chronic stress, and that stress-induced variations in mPFC levels of miR-218 could be detected in blood. We propose that blood expression of miR-218 might serve as potential readout of vulnerability to stress and as a proxy of mPFC function.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / blood
  • Biomarkers / metabolism
  • Down-Regulation
  • Male
  • Mice
  • MicroRNAs / biosynthesis*
  • MicroRNAs / blood
  • Prefrontal Cortex / metabolism
  • Social Defeat*
  • Stress, Psychological / blood
  • Stress, Psychological / genetics*
  • Up-Regulation


  • Biomarkers
  • MIRN218 microRNA, mouse
  • MicroRNAs