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Depression: miR135 promotes resilience

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A new study suggests that microRNA 135 (miR135) is protective against stress-induced depression-like behaviors and mediates the effects of some antidepressant drugs (Neuron 83, 344–360).

Dysregulation of serotonin (5HT) signaling is strongly implicated in mood disorders. By comparing the miR profiles of 5HT and non-5HT mouse midbrain raphe nuclei (RN) neurons, Orna Issler and her colleagues identified miR135 as a repressor of two genes associated with 5HT signaling. Treatment with 5HT-targeting antidepressants increased expression of miR135a, the predominant allele in the mouse brain. Overexpression of miR135a in 5HT neurons protected against increased anxiety and depression-like behaviors in mice following chronic social defeat stress. miR135a overexpression also decreased 5HT levels and increased 5HT metabolism in the mouse brain, consistent with increased firing of 5HT neurons. Conversely, reducing miR135a levels in the RN exacerbated anxiety-like behavior and blunted the response to antidepressant treatment.

The authors found that circulating miR135a is decreased in depressed patients and increased in depressed patients that underwent cognitive behavioral therapy. Post-mortem analysis also identified downregulation of mi135a in the brains of depressed suicide victims. This suggests that mi135a regulates normal 5HT tone and may be a promising drug target or biomarker for depression.

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Carr, F. Depression: miR135 promotes resilience. Nat Med 20, 991 (2014). https://doi.org/10.1038/nm.3691

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