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bioRxiv · 10.1101/589325

MiR-218: A Molecular Switch and Potential Biomarker of Susceptibility to Stress

Torres-Berrio, A.·Nouel, D.·Cuesta, S.·Parise, E. M.·Restrepo-Lozano, J. M.·Larochelle, P.·Nestler, E. J.·Flores, C.
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Abstract

Low miR-218 expression in the medial prefrontal cortex (mPFC) is a consistent trait of depression. Here we assessed whether miR-218 in the mPFC confers resilience or susceptibility to depression-like behaviors in adult mice, using the chronic social defeat stress (CSDS) model of depression. We also investigated whether stress-induced variations of miR-218 expression in the mPFC can be detected in blood. We find that downregulation of miR-218 in the mPFC increases susceptibility to a single session of social defeat, whereas overexpression of miR-218 selectively in mPFC pyramidal neurons promotes resilience to CSDS and prevents stress-induced morphological alterations to those neurons. After CSDS, susceptible mice have low levels of miR-218 in the blood as compared to control or resilient groups. We show further that up-and downregulation of miR-218 levels specifically in the mPFC correlates with miR-218 expression in blood. Our results suggest that miR-218 in the adult mPFC might function as a molecular switch that determines susceptibility versus resilience to chronic stress, and that stress-induced variations in mPFC levels of miR-218 could be detected in blood. We propose that blood expression of miR-218 might serve as potential readout of vulnerability to stress and as a proxy of mPFC function.

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Torres-Berrio, A., Nouel, D., Cuesta, S., Parise, E. M., Restrepo-Lozano, J. M., Larochelle, P., Nestler, E. J., Flores, C.. 2019-03-28. MiR-218: A Molecular Switch and Potential Biomarker of Susceptibility to Stress. https://doi.org/10.1101/589325

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