Amygdalar MicroRNA-15a Is Essential for Coping with Chronic Stress.
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.
Department of Neurobiology, Weizmann Institute of Science, Rehovot 76100, Israel; Department of Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Munich, Bavaria 80804, Germany.
Naama
N
Volk
Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Bavaria 80804, Germany.
Julius C
JC
Pape
Department of Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Munich, Bavaria 80804, Germany.
Mareen
M
Engel
Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Bavaria 80804, Germany; Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC 27710, USA.
Anthony S
AS
Zannas
Biological Psychiatry Unit, IRCCS Fatebenefratelli, University of Brescia, 25121 Brescia, Italy.
Nadia
N
Cattane
Biological Psychiatry Unit, IRCCS Fatebenefratelli, University of Brescia, 25121 Brescia, Italy; Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London WC2R 2LS, UK.
Annamaria
A
Cattaneo
Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Bavaria 80804, Germany; Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30322, USA.
Elisabeth B
EB
Binder
Department of Neurobiology, Weizmann Institute of Science, Rehovot 76100, Israel; Department of Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Munich, Bavaria 80804, Germany. Electronic address: alon.chen@weizmann.ac.il.
Alon
A
Chen
D000223:Adaptation, Psychological; D000679:Amygdala / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001007:Anxiety / Q000150:complications / Q000235:genetics; D060565:Argonaute Proteins / Q000378:metabolism; D001483:Base Sequence; D001522:Behavior, Animal; D002908:Chronic Disease; D005786:Gene Expression Regulation / Q000187:drug effects; D055785:Gene Knockdown Techniques; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D008297:Male; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013315:Stress, Psychological / Q000150:complications / Q000235:genetics*; D022021:Tacrolimus Binding Proteins / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014947:Wounds and Injuries / Q000150:complications / Q000235:genetics; D000099159:Tacrolimus Binding Protein 5
D060565:Argonaute Proteins; D005938:Glucocorticoids; D035683:MicroRNAs; D012333:RNA, Messenger; D022021:Tacrolimus Binding Proteins; D000099159:Tacrolimus Binding Protein 5; C505361:MIRN15 microRNA, human; C570833:Mirn15 microRNA, mouse
Ago2; FKBP5; amygdala; anxiety; childhood trauma; chronic stress; early life stress; microRNA-15a; stress adaption; stress-related psychopathologies