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

• Type of Material: Article
• 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
• Language: English
• Date: 2016-11-08
• Publisher: Elsevier (Cell Press): OAJ
• Publication Version: Final Published Version
• Copyright Statement: © 2016 The Authors
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.celrep.2016.10.038
• Title of Journal or Parent Work: Cell Reports
• ISSN: 2211-1247
• Volume: 17
• Issue: 7
• Start Page: 1882
• End Page: 1891
• Grant/Funding Information: The human studies were supported by the Behrens-Weise Foundation (to E.B.B.) and a European Research Council starting grant (grant number 281338, GxE molmech) within the FP7 framework (to E.B.B.).; This work is supported by: The Max Planck Foundation; an FP7 grant from the European Research Council (260463); the I-CORE Program of the Planning and Budget Committee and the Israel Science Foundation (grant no. 1916/12); a research grant from the Israel Science Foundation (1351/12)
• Keywords: amygdala; chronic stress; anxiety; early life stress; stress-related psychopathologies; FKBP5; childhood trauma; microRNA-15a; Ago2; stress adaption
• Research Categories: Biology, Neuroscience; Psychology, Clinical

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.