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Abstract:
MicroRNAs are important regulators of gene expression and associated
with stress-related psychiatric disorders. Here, we report that exposing
mice tochronic 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-15ain
stress adaptation and the pathogenesis of stress-related
psychopathologies.
