• Brietta Gerrard, Vaibhav Singh, Olena Babenko, Isabelle Gauthier, Wee Yong V V Hotchkiss Brain Institute, Departments of Clinical Neurosciences and Oncology, University of Calgary, Calgary, AB T2N 4N1 Canada., Igor Kovalchuk, Artur Luczak, and Metz Gerlinde A S GAS Canadian Centre for Behavioural Neuroscience, Department of Neuroscience, University of Lethbridge, Lethbridge, AB T1K 3M4, Canada. Electronic addre.
• Canadian Centre for Behavioural Neuroscience, Department of Neuroscience, University of Lethbridge, Lethbridge, AB T1K 3M4, Canada.
• Neuroscience. 2017 Sep 17; 359: 299-307.

AbstractThe causal factors determining the onset and severity of multiple sclerosis (MS) are not well understood. Here, we investigated the influence of chronic stress on clinical symptoms, metabolic and epigenetic manifestations of experimental autoimmune encephalomyelitis (EAE), a common animal model of MS. Lewis rats were immunized for monophasic EAE with MBP69-88 and were exposed to chronic stress for 37days starting 7days prior to immunization. The exposure to stress accelerated and exacerbated the clinical symptoms of EAE. Both stress and EAE also disrupted metabolic status as indicated by trace elemental analysis in body hair. Stress particularly exacerbated chlorine deposition in EAE animals. Moreover, deep sequencing revealed a considerable impact of stress on microRNA expression in EAE. EAE by itself upregulated microRNA expression in lumbar spinal cord, including miR-21, miR-142-3p, miR-142-5p, miR-146a, and miR-155. Stress in EAE further up-regulated miR-16, miR-146a and miR-155 levels. The latter two microRNAs are recognized biomarkers of human MS. Thus, stress may synergistically exacerbate severity of EAE by altering epigenetic regulatory pathways. The findings suggest that stress may represent a significant risk factor for symptomatic deterioration in MS. Stress-related metabolic and microRNA signatures support their value as biomarkers for predicting the risk and severity of MS.Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

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