miR-135a and miR-124 in Stress Response

In the brain, stress-related information from all sensory systems is conveyed to limbic brain structures. In particular, the amygdala is considered an important node for stress response integration. Adaptation to stress involves highly coordinated changes in gene expression, involving different layers of post-transcriptional regulation. In order to study how acute stress affects miRNAs expression in amygdala we analyzed the miRNA profile after two hours of mouse restraint. We found that miR-135a and miR-124 were negatively regulated. We identified the mineralocorticoid receptor (MR), one of the key effectors of the corticosteroid cascade, as a target of both miRNAs. The increased levels of the amygdala MR protein after two hours of restraint negatively correlate with miR-135a and miR-124 expression. We will present new data showing that miR-135a targets also Complexin 1 and 2, two major components of synaptic vesicle fusion complex. Our data suggest that the role of miR-135a and miR-124 on early stress response is achieved by the coordinated regulation of multiple targets that function on corticosteroid signaling, neurotransmitter activation and synaptic plasticity.