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

• Published in: Cell reports (Cambridge) Vol. 17; no. 7; pp. 1882 - 1891
• Main Authors: Volk, Naama, Pape, Julius C., Engel, Mareen, Zannas, Anthony S., Cattane, Nadia, Cattaneo, Annamaria, Binder, Elisabeth B., Chen, Alon
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 08.11.2016; Cell Press; Elsevier
• Subjects: Adaptation, Psychological; Ago2; amygdala; Amygdala - drug effects; Amygdala - metabolism; Animals; anxiety; Anxiety - complications; Anxiety - genetics; Argonaute Proteins - metabolism; Base Sequence; Behavior, Animal; childhood trauma; Chronic Disease; chronic stress; early life stress; FKBP5; Gene Expression Regulation - drug effects; Gene Knockdown Techniques; Glucocorticoids - pharmacology; Humans; Male; Mice, Inbred C57BL; microRNA-15a; MicroRNAs - genetics; MicroRNAs - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; stress adaption; Stress, Psychological - complications; Stress, Psychological - genetics; stress-related psychopathologies; Tacrolimus Binding Proteins - genetics; Tacrolimus Binding Proteins - metabolism; Transcription, Genetic - drug effects; Wounds and Injuries - complications; Wounds and Injuries - genetics; anxiety; childhood trauma; amygdala; microRNA-15a; stress-related psychopathologies; Ago2; chronic stress; stress adaption; early life stress; FKBP5
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2016.10.038

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. [Display omitted] •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.