title: Neuro-Epigenetic Indications of Acute Stress Response in Humans: The Case of MicroRNA-29c.
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 stress-induced functional neural alterations reflecting regulatory processes. Such a multi-level model may hold the key for future personalized intervention in stress psychopathology.
authors.affiliation: Functional Brain Center, Wohl Institute for Advanced Imaging, Sourasky Medical Center, Tel Aviv, Israel.|Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.|Sagol School of Neuroscience; Tel-Aviv University, Tel Aviv, Israel.
authors.forename: Sharon
authors.initials: S
authors.lastname: Vaisvaser
authors.affiliation: Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Shira
authors.initials: S
authors.lastname: Modai
authors.affiliation: Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Luba
authors.initials: L
authors.lastname: Farberov
authors.affiliation: Functional Brain Center, Wohl Institute for Advanced Imaging, Sourasky Medical Center, Tel Aviv, Israel.|School of Psychological Sciences, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Tamar
authors.initials: T
authors.lastname: Lin
authors.affiliation: Functional Brain Center, Wohl Institute for Advanced Imaging, Sourasky Medical Center, Tel Aviv, Israel.|Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Haggai
authors.initials: H
authors.lastname: Sharon
authors.affiliation: Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Avital
authors.initials: A
authors.lastname: Gilam
authors.affiliation: Department of Neurobiology Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Naama
authors.initials: N
authors.lastname: Volk
authors.affiliation: Center for Depression, Anxiety and Stress Research, McLean Hospital, Harvard medical School, Boston, Massachussetts, United States of America.
authors.forename: Roee
authors.initials: R
authors.lastname: Admon
authors.affiliation: Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Liat
authors.initials: L
authors.lastname: Edry
authors.affiliation: Division of Mental Health, Medical Corps, IDF, Ramat Gan, Israel.
authors.forename: Eyal
authors.initials: E
authors.lastname: Fruchter
authors.affiliation: School of Psychological Sciences, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Ilan
authors.initials: I
authors.lastname: Wald
authors.affiliation: Sagol School of Neuroscience; Tel-Aviv University, Tel Aviv, Israel.|School of Psychological Sciences, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Yair
authors.initials: Y
authors.lastname: Bar-Haim
authors.affiliation: Sagol School of Neuroscience; Tel-Aviv University, Tel Aviv, Israel.|School of Education, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Tarrasch
authors.affiliation: Department of Neurobiology Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Alon
authors.initials: A
authors.lastname: Chen
authors.affiliation: Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.|Sagol School of Neuroscience; Tel-Aviv University, Tel Aviv, Israel.
authors.forename: Noam
authors.initials: N
authors.lastname: Shomron
authors.affiliation: Functional Brain Center, Wohl Institute for Advanced Imaging, Sourasky Medical Center, Tel Aviv, Israel.|Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.|Sagol School of Neuroscience; Tel-Aviv University, Tel Aviv, Israel.|School of Psychological Sciences, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Talma
authors.initials: T
authors.lastname: Hendler
mesh_terms: D001921:Brain / Q000503:physiopathology*; D044127:Epigenesis, Genetic; D059907:Functional Neuroimaging; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009434:Neural Pathways / Q000503:physiopathology; D013315:Stress, Psychological / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D055815:Young Adult
chemical_list: C532045:MIRN29a microRNA, human; D035683:MicroRNAs