Neuro-epigenetic indications of acute stress response in humans: The case of microRNA-29c

Sharon Vaisvaser, Shira Modai, Luba Farberov, Tamar Lin, Haggai Sharon, Avital Gilam, Naama Volk, Roee Admon, Liat Edry, Eyal Fruchter, Ilan Wald, Yair Bar-Haim, Ricardo Tarrasch, Alon Chen, Noam Shomron, Talma Hendler

Research output: Contribution to journalArticlepeer-review

Abstract

Stress research has progressively become more integrative in nature, seeking to unfold crucial relations between the different phenotypic levels of stress manifestations. This study sought to unravel stress-induced variations in expression of human microRNAs sampled in peripheral blood mononuclear cells and further assess their relationship with neuronal and psychological indices. We obtained blood samples from 49 healthy male participants before and three hours after performing a social stress task, while undergoing functional magnetic resonance imaging (fMRI). A seed-based functional connectivity (FC) analysis was conducted for the ventro-medial prefrontal cortex (vmPFC), a key area of stress regulation. Out of hundreds of microRNAs, a specific increase was identified in microRNA-29c (miR-29c) expression, corresponding with both the experience of sustained stress via self-reports, and alterations in vmPFC functional connectivity. Explicitly, miR-29c expression levels corresponded with both increased connectivity of the vmPFC with the anterior insula (aIns), and decreased connectivity of the vmPFC with the left dorso-lateral prefrontal cortex (dlPFC). Our findings further revealed that miR-29c mediates an indirect path linking enhanced vmPFC-AIns connectivity during stress with subsequent experiences of sustained stress. The correlative patterns of miR-29c expression and vmPFC FC, along with the mediating effects on subjective stress sustainment and the presumed localization of miR-29c in astrocytes, together point to an intriguing assumption; miR-29c may serve as a biomarker in the blood for stressinduced functional neural alterations reflecting regulatory processes. Such a multi-level model may hold the key for future personalized intervention in stress psychopathology.

Original languageEnglish
Article numbere0146236
JournalPLoS ONE
Volume11
Issue number1
DOIs
StatePublished - 5 Jan 2016
Externally publishedYes

Bibliographical note

Funding Information:
This research was supported by the U.S. Department of Defense award number W81XWH-11-2-0008, Israel Ministry of Defense, Tel-Aviv University, and the I-CORE Program of the Planning and Budgeting Committee and The Israel Science Foundation (Grant No. 51/11). The authors thank Harel Zalts, Eyal Mor and Sharon Tzadok for their assistance and Vicki Myers and Aliya Solski for their help in editing the manuscript.

Publisher Copyright:
© 2016 Vaisvaser et al.This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

ASJC Scopus subject areas

  • General

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