Amygdalar MicroRNA-15a Is Essential for Coping with Chronic Stress

Cell Rep. 2016 Nov 8;17(7):1882-1891. doi: 10.1016/j.celrep.2016.10.038.

Abstract

MicroRNAs are important regulators of gene expression and associated with stress-related psychiatric disorders. Here, we report that exposing mice to chronic stress led to a specific increase in microRNA-15a levels in the amygdala-Ago2 complex and a concomitant reduction in the levels of its predicted target, FKBP51, which is implicated in stress-related psychiatric disorders. Reciprocally, mice expressing reduced levels of amygdalar microRNA-15a following exposure to chronic stress exhibited increased anxiety-like behaviors. In humans, pharmacological activation of the glucocorticoid receptor, as well as exposure to childhood trauma, was associated with increased microRNA-15a levels in peripheral blood. Taken together, our results support an important role for microRNA-15a in stress adaptation and the pathogenesis of stress-related psychopathologies.

Keywords: Ago2; FKBP5; amygdala; anxiety; childhood trauma; chronic stress; early life stress; microRNA-15a; stress adaption; stress-related psychopathologies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Psychological*
  • Amygdala / drug effects
  • Amygdala / metabolism*
  • Animals
  • Anxiety / complications
  • Anxiety / genetics
  • Argonaute Proteins / metabolism
  • Base Sequence
  • Behavior, Animal
  • Chronic Disease
  • Gene Expression Regulation / drug effects
  • Gene Knockdown Techniques
  • Glucocorticoids / pharmacology
  • Humans
  • Male
  • Mice, Inbred C57BL
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Stress, Psychological / complications
  • Stress, Psychological / genetics*
  • Tacrolimus Binding Proteins / genetics
  • Tacrolimus Binding Proteins / metabolism
  • Transcription, Genetic / drug effects
  • Wounds and Injuries / complications
  • Wounds and Injuries / genetics

Substances

  • Argonaute Proteins
  • Glucocorticoids
  • MIRN15 microRNA, human
  • MicroRNAs
  • Mirn15 microRNA, mouse
  • RNA, Messenger
  • Tacrolimus Binding Proteins
  • tacrolimus binding protein 5