MiR-218: a molecular switch and potential biomarker of susceptibility to stress.

TitleMiR-218: a molecular switch and potential biomarker of susceptibility to stress.
Publication TypeJournal Article
Year of Publication2019
AuthorsTorres-Berrío A, Nouel D, Cuesta S, Parise EM, Restrepo-Lozano JMaria, Larochelle P, Nestler EJ, Flores C
JournalMol Psychiatry
Date Published2019 Apr 12
ISSN1476-5578
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 blood, as compared with control or resilient groups. We show further that upregulation and downregulation of miR-218 levels specifically in the mPFC correlate 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 vs. 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.

DOI10.1038/s41380-019-0421-5
Alternate JournalMol. Psychiatry
PubMed ID30980043
Grant ListMOP-74709 / / Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada) /
R01 DA037911 / DA / NIDA NIH HHS / United States
R01DA037911 / / U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (NIDA) /
P50MH096890 / / U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) /
R01MH051399 / / U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) /