title: MicroRNAs as biomarkers of resilience or vulnerability to stress.
abstract: Identifying novel biomarkers of resilience or vulnerability to stress could provide valuable information for the prevention and treatment of stress-related psychiatric disorders. To investigate the utility of blood microRNAs as biomarkers of resilience or vulnerability to stress, microRNAs were assessed before and after 7days of chronic social defeat in rats. Additionally, microRNA profiles of two important stress-regulatory brain regions, the medial prefrontal cortex (mPFC) and basolateral amygdala (BLA), were assessed. Rats that displayed vulnerability to subsequent chronic stress exhibited reductions in circulating miR-24-2-5p, miR-27a-3p, miR-30e-5p, miR-3590-3p, miR-362-3p, and miR-532-5p levels. In contrast, rats that became resilient to stress displayed reduced levels of miR-139-5p, miR-28-3p, miR-326-3p, and miR-99b-5p compared to controls. In the mPFC, miR-126a-3p and miR-708-5p levels were higher in vulnerability compared to resilient rats. In the BLA, 77 microRNAs were significantly altered by stress but none were significantly different between resilient and vulnerable animals. These results provide proof-of-principle that assessment of circulating microRNAs is useful in identifying individuals who are vulnerable to the effects of future stress or individuals who have become resilient to the effects of stress. Furthermore, these data suggest that microRNAs in the mPFC but not in the BLA are regulators of resilience/vulnerability to stress.
authors.affiliation: Department of Anesthesiology, Children's Hospital of Philadelphia, United States.
authors.forename: R J
authors.initials: RJ
authors.lastname: Chen
authors.affiliation: Department of Anesthesiology, Children's Hospital of Philadelphia, United States.
authors.forename: G
authors.initials: G
authors.lastname: Kelly
authors.affiliation: Department of Anesthesiology, Children's Hospital of Philadelphia, United States.
authors.forename: A
authors.initials: A
authors.lastname: Sengupta
authors.affiliation: Department of Anesthesiology, Children's Hospital of Philadelphia, United States.
authors.forename: W
authors.initials: W
authors.lastname: Heydendael
authors.affiliation: Department of Anesthesiology, Children's Hospital of Philadelphia, United States.
authors.forename: B
authors.initials: B
authors.lastname: Nicholas
authors.affiliation: Department of Anesthesiology, Children's Hospital of Philadelphia, United States.
authors.forename: S
authors.initials: S
authors.lastname: Beltrami
authors.affiliation: Department of Anesthesiology, Children's Hospital of Philadelphia, United States.
authors.forename: S
authors.initials: S
authors.lastname: Luz
authors.affiliation: Department of Biology, University of Pennsylvania, United States.
authors.forename: L
authors.initials: L
authors.lastname: Peixoto
authors.affiliation: Department of Biology, University of Pennsylvania, United States.
authors.forename: T
authors.initials: T
authors.lastname: Abel
authors.affiliation: Department of Anesthesiology, Children's Hospital of Philadelphia, United States; Department of Anesthesiology, University of Pennsylvania, Perelman School of Medicine, United States. Electronic address: bhatnagars@email.chop.edu.
authors.forename: S
authors.initials: S
authors.lastname: Bhatnagar
mesh_terms: D000679:Amygdala / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D046228:Microarray Analysis; D017397:Prefrontal Cortex / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000502:physiology; D020127:Recovery of Function / Q000502:physiology*; D012930:Social Dominance; D013315:Stress, Psychological / Q000378:metabolism* / Q000473:pathology*; D013997:Time Factors
chemical_list: D015415:Biomarkers; D035683:MicroRNAs; D012333:RNA, Messenger
keywords: amygdala; biomarker; blood; microRNA; prefrontal cortex; social stress