Neuroprotective role of neuronal miR-27a and miR-223 during inflammation
Author(s): ,
B. Morquette
Affiliations:
Neurology and Neurosurgery, Montreal Neurological Institute, McGill University
,
C. Juzwik
Affiliations:
Neurology and Neurosurgery, Montreal Neurological Institute, McGill University
,
M. Charabati
Affiliations:
Neuroscience, Centre de Recherche du Centre Hospitalier de l`Universite de Montreal, Montreal, QC
,
Y. Zhang
Affiliations:
Neurology and Neurosurgery, Montreal Neurological Institute, McGill University
,
S. Drake
Affiliations:
Neurology and Neurosurgery, Montreal Neurological Institute, McGill University
,
M.-A. Lecuyer
Affiliations:
Neuroscience, Centre de Recherche du Centre Hospitalier de l`Universite de Montreal, Montreal, QC
,
D. Galloway
Affiliations:
Division of BioMedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John, NL
,
O. de Faria Junior
Affiliations:
Neurology and Neurosurgery, Montreal Neurological Institute, McGill University
,
M.-P. Girouard
Affiliations:
Neurology and Neurosurgery, Montreal Neurological Institute, McGill University
,
C. Moore
Affiliations:
Division of BioMedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John, NL
,
A. O-Bar
Affiliations:
Microbiology and Immunology, Montreal Neurological Institute, McGill University, Montreal, QC, Canada
,
A. Prat
Affiliations:
Neuroscience, Centre de Recherche du Centre Hospitalier de l`Universite de Montreal, Montreal, QC
A. Fournier
Affiliations:
Neurology and Neurosurgery, Montreal Neurological Institute, McGill University
ECTRIMS Online Library. Morquette B. Oct 12, 2018; 228935; P1095
Barbara Morquette
Barbara Morquette
Contributions
Abstract

Abstract: P1095

Type: Poster Sessions

Abstract Category: Pathology and pathogenesis of MS - Neurodegeneration

Introduction: Multiple sclerosis is an autoimmune disease characterized by inflammatory demyelination and neurodegeneration occurring in the brain, the spinal cord and the optic nerve. Our comprehension of how immune cells and their by-products influence the degeneration of CNS neurons is not well known. The aim of this study is to investigate whether neuronal microRNAs, powerful regulators of gene expression, are modulated in an inflammatory milieu and their functional role during neurodegeneration.
Methods: Experimental Autoimmune Encephalomyelitis (EAE) was induced in C57Bl/6 mice with MOG35-55 peptide in emulsion of incomplete Freund's adjuvant. Non-phosphorylated neurofilament labelling by iDisco was used to monitor axonal defects in whole mount cleared EAE optic nerves across the disease course. To assess neuronal expression of microRNAs, neurons were laser capture micro-dissected. The effects of two microRNAs on axonal degeneration were assessed in vitro, and their mRNA targets identified by in silico analysis.
Results: Our results show early and robust axonal swellings in EAE optic nerves, which correlate with the presence of immune cell infiltration. We identified miR-27a-3p and miR-223-3p upregulated in the neurons of EAE mice relative to naïve mice. In parallel, cortical neurons stimulated in vitro with peripheral blood mononuclear cell conditioned media (PBMC-CM) showed a similar increase. Overexpression of these microRNAs demonstrated neuroprotective properties in an in vitro assay. By in silico analysis we identified the glutamate receptor (GluR) pathway enriched in miR-27a-3p and miR-223-3p targets. Antagonism of the GluR pathway rescued PBMC-CM induced degeneration.
Conclusions: Here we show that neuronal miR-27a-3p and miR-223-3p are regulated during inflammation and can mediate neuroprotection in vitro. Thus, our data suggests a correlation between axonal impairments and modified expression of microRNAs in EAE.
Disclosure: Source of funding: This investigation is funded by Multiple Sclerosis Society of Canada (MSSC). Barbara Morquette is funded by endMS Postdoctoral Fellowship Award from the Multiple Sclerosis Society of Canada and Fonds de la recherche du Québec- Santé.
Disclosure: Barbara Morquette: nothing to disclose; Camille Juzwik: nothing to disclose; Marc Charabati: nothing to disclose; Yang Zhang: nothing to disclose; Sienna Drake: nothing to disclose; Marc-André Lécuyer: nothing to disclose; Omar de Faria Junior: nothing to disclose Marie-Pier Girouard; Dylan Galloway: nothing to disclose; Craig Moore5, Amit O-Bar: nothing to disclose; Alexandre Prat: nothing to disclose; Alyson E Fournier: nothing to disclose.

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