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Cited by 79MicroRNA in disease regulationTreatment of Major DepressionStress Responses and Cortisol

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

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Torres-Berrío, Angélica, Nouel, Dominique, Cuesta, Santiago, Parise, Eric M., Restrepo-Lozano, José María, Larochelle, Pier, Nestler, Eric J., Flores, Cecilia·2020·Molecular Psychiatry
DOI 10.1038/s41380-019-0421-5PMC PMC6790160

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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 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.

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  • Low miR-218 expression may influence synapse formation and synaptic plasticity of the mPFC by repressing DCC in mouse models of social defeat stress.

    “Low miR-218 expression may influence synapse formation and synaptic plasticity of the mPFC by repressing the gene expression of Netrin-1 guidance cue receptor gene DCC in mouse models of social defeat stress.266”

    From Epigenetic regulation in major depression and other stress-related disorders: molecular mechanisms, clinical relevance and therapeutic potential (2023) · cites this paper as [266]

    The Discussion (page not provided) says miR-218 represses DCC, but reduced miR-218 is associated with increased DCC expression—not repression. The Results and Discussion also report that miR-218 overexpression increased thin dendritic-spine density in mice exposed to chronic social defeat stress. (LLM, conf=0.88)

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Cited by

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Authors
Torres-Berrío, A., Nouel, D., Cuesta, S., Parise, E. M., Restrepo-Lozano, J. M., Larochelle, P., Nestler, E. J., & Flores, C.
Affiliations
  • Douglas Mental Health University Institute (CA)
  • Icahn School of Medicine at Mount Sinai (US)
Corresponding author
Flores, Cecilia
ORCID
Venue
Molecular Psychiatry
Publisher
Springer Science and Business Media LLC
Published
2019-04-12
Volume
25
Issue
5
Pages
951-964
ISSN
  • 1359-4184 (ISSN-L)
  • 1476-5578
DOI
10.1038/s41380-019-0421-5
PMC
PMC6790160
OpenAlex
W2923435669
Cited by
79
References
11
Citations by year
2026: 2 · 2025: 16 · 2024: 9 · 2023: 17 · 2022: 8 · 2021: 14 · 2020: 12 · 2019: 1
FWCI
2.71
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecular Psychiatry (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Gouvernement du Canada | Canadian Institutes of Health Research (MOP-74709)
  • U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (R01DA037911)
  • U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (P50MH096890, R01MH051399)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Keywords
miR-218, microRNA, depression, chronic social defeat stress, depression-like behavior, resilience, medial prefrontal cortex, pyramidal neurons, blood biomarkers, molecular switches
MeSH terms
Social Defeat, Animals, Male, Stress, Psychological, Biomarkers, Down-Regulation, Up-Regulation, Prefrontal Cortex, MicroRNAs, Mice

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