Neuro-Epigenetic Indications of Acute Stress Response in Humans: The Case of MicroRNA-29c

• Published in: PloS one 2016-01, Vol.11 (1), p.e0146236-e0146236
• Main Authors: Vaisvaser, Sharon, Modai, Shira, Farberov, Luba, Lin, Tamar, Sharon, Haggai, Gilam, Avital, Volk, Naama, Admon, Roee, Edry, Liat, Fruchter, Eyal, Wald, Ilan, Bar-Haim, Yair, Tarrasch, Ricardo, Chen, Alon, Shomron, Noam, Hendler, Talma
• Format: Article
• Language: English
• Subjects: Acute stress disorder; Alterations; Astrocytes; Biomarkers; Blood; Brain - physiopathology; Brain research; Care and treatment; Connectivity; Epigenesis, Genetic; Epigenetic inheritance; Epigenetics; Functional magnetic resonance imaging; Functional Neuroimaging; Gene expression; Humans; Laws, regulations and rules; Leukocytes (mononuclear); Localization; Magnetic resonance; Magnetic Resonance Imaging; Male; Medicine; Memory; MicroRNA; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; miRNA; Neural networks; Neural Pathways - physiopathology; Neurobiology; Neuroimaging; Neurophysiology; Neurosciences; Peripheral blood mononuclear cells; Prefrontal cortex; Psychopathology; Ribonucleic acid; Risk factors; RNA; Schizophrenia; Social interactions; Stress; Stress, Psychological - genetics; Stress, Psychological - metabolism; Stress, Psychological - physiopathology; Stresses; Young Adult
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0146236

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 stress-induced functional neural alterations reflecting regulatory processes. Such a multi-level model may hold the key for future personalized intervention in stress psychopathology.