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

Summary 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.

Graphical Abstract

Highlights • miR-15a levels are elevated in the amygdala-Ago2 complex following chronic stress • miR-15a targets FKBP51 and affects behavioral responses to stressful challenges • miR-15a is elevated in peripheral human blood following dexamethasone exposure • miR-15a is elevated in peripheral human blood of patients exposed to childhood trauma

Volk et al. reveal an important role for microRNA-15a in coping with chronic stress, with amygdala-specific manipulation affecting behavioral responses to stressful challenge. Individuals exposed to childhood trauma exhibit increased levels of miR-15a in their peripheral blood, suggesting a target for the treatment of stress-related psychopathologies.