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

• Authors: Naama Volk, Weizmann Institute of Science; Julius C. Pape, Max Planck Institute of Psychiatry; Mareen Engel, Max Planck Institute of Psychiatry; Anthony S. Zannas, Max Planck Institute of Psychiatry; Nadia Cattane, University of Brescia; Annamaria Cattaneo, University of Brescia; Elisabeth Binder, Emory University; Alon Chen, Weizmann Institute of Science
• Journal Title: Cell Reports
• Volume: Volume 17, Number 7
• Publisher: Elsevier (Cell Press): OAJ | 2016-11-08, Pages 1882-1891
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1016/j.celrep.2016.10.038
• Subjects: Biology, Neuroscience; Psychology, Clinical
• Keywords: Ago2; FKBP5; amygdala; anxiety; childhood trauma; chronic stress; early life stress; microRNA-15a; stress adaption; stress-related psychopathologies

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.