Title: MicroRNAs as disease progression biomarkers and therapeutic targets in experimental autoimmune encephalomyelitis model of multiple sclerosis

Abstract

Multiple sclerosis is an autoimmune neurodegenerative disease of the central nervous system characterized by pronounced inflammatory infiltrates entering the brain, spinal cord and optic nerve leading to demyelination. Focal demyelination is associated with relapsing-remitting multiple sclerosis, while progressive forms of the disease show axonal degeneration and neuronal loss. The tests currently used in the clinical diagnosis and management of multiple sclerosis have limitations due to specificity and sensitivity. MicroRNAs (miRNAs) are dysregulated in many diseases and disorders including demyelinating and neuroinflammatory diseases. A review of recent studies with the experimental autoimmune encephalomyelitis animal model (mostly female mice 6–12 weeks of age) has confirmed miRNAs as biomarkers of experimental autoimmune encephalomyelitis disease and importantly at the pre-onset (asymptomatic) stage when assessed in blood plasma and urine exosomes, and spinal cord tissue. The expression of certain miRNAs was also dysregulated at the onset and peak of disease in blood plasma and urine exosomes, brain and spinal cord tissue, and at the post-peak (chronic) stage of experimental autoimmune encephalomyelitis disease in spinal cord tissue. Therapies using miRNA mimics or inhibitors were found to delay the induction and alleviate the severity of experimental autoimmune encephalomyelitis disease. Interestingly, experimental autoimmune encephalomyelitis disease severity was reducedmore » by overexpression of miR-146a, miR-23b, miR-497, miR-26a, and miR-20b, or by suppression of miR-182, miR-181c, miR-223, miR-155, and miR873. Further studies are warranted on determining more fully miRNA profiles in blood plasma and urine exosomes of experimental autoimmune encephalomyelitis animals since they could serve as biomarkers of asymptomatic multiple sclerosis and disease course. Additionally, studies should be performed with male mice of a similar age, and with aged male and female mice.« less

Authors:

Martinez, Bridget ^[1]; Peplow, PhilipV ^[2]

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+ Show Author Affiliations

1. Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Chemistry Division. Physical Chemistry and Applied Spectroscopy; St. Georges Univ. (Grenada). School of Medicine. Dept. of Medicine
2. Univ. of Otago, Dunedin (New Zealand). Dept. of Anatomy

Publication Date:

Fri Apr 03 00:00:00 EDT 2020

Research Org.:

Triad National Security, LLC, Los Alamos, NM (United States)

Sponsoring Org.:

USDOE Office of Science (SC)

OSTI Identifier:

1815782

Grant/Contract Number:  

89233218CNA000001

Resource Type:

Accepted Manuscript

Journal Name:

Neural Regeneration Research

Additional Journal Information:

Journal Volume: 15; Journal Issue: 10; Journal ID: ISSN 1673-5374

Publisher:

Chinese Association of Rehabilitation Medicine (CARM)

Country of Publication:

United States

Language:

English

Subject:

59 BASIC BIOLOGICAL SCIENCES; animal model; blood plasma; blood serum; brain tissue; disease biomarkers; experimental autoimmune; encephalomyelitis; microRNAs; multiple sclerosis; spinal cord; therapeutic targets; urine exosomes