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MicroRNA-223 protects neurons from degeneration in experimental autoimmune encephalomyelitis.
Brain. 2019 10 01; 142(10):2979-2995.B

Abstract

Multiple sclerosis is a chronic inflammatory, demyelinating, and neurodegenerative disease affecting the brain, spinal cord and optic nerves. Neuronal damage is triggered by various harmful factors that engage diverse signalling cascades in neurons; thus, therapeutic approaches to protect neurons will need to focus on agents that can target multiple biological processes. We have therefore focused our attention on microRNAs: small non-coding RNAs that primarily function as post-transcriptional regulators that target messenger RNAs and repress their translation into proteins. A single microRNA can target many functionally related messenger RNAs making microRNAs powerful epigenetic regulators. Dysregulation of microRNAs has been described in many neurodegenerative diseases including multiple sclerosis. Here, we report that two microRNAs, miR-223-3p and miR-27a-3p, are upregulated in neurons in the experimental autoimmune encephalomyelitis mouse model of CNS inflammation and in grey matter-containing multiple sclerosis lesions. Prior work has shown peripheral blood mononuclear cell conditioned media causes sublethal degeneration of neurons in culture. We find overexpression of miR-27a-3p or miR-223-3p protects dissociated cortical neurons from condition media mediated degeneration. Introduction of miR-223-3p in vivo in mouse retinal ganglion cells protects their axons from degeneration in experimental autoimmune encephalomyelitis. In silico analysis revealed that messenger RNAs involved in glutamate receptor signalling are enriched as miR-27a-3p and miR-223-3p targets. We observe that antagonism of NMDA and AMPA type glutamate receptors protects neurons from condition media dependent degeneration. Our results suggest that miR-223-3p and miR-27a-3p are upregulated in response to inflammation to mediate a compensatory neuroprotective gene expression program that desensitizes neurons to glutamate by targeting messenger RNAs involved in glutamate receptor signalling.

Authors+Show Affiliations

McGill University - Montréal Neurological Institute, Montréal, QC, Canada.McGill University - Montréal Neurological Institute, Montréal, QC, Canada.McGill University - Montréal Neurological Institute, Montréal, QC, Canada.CHUM research centre - Université de Montreal, Montréal, QC, Canada.McGill University - Montréal Neurological Institute, Montréal, QC, Canada.Institute for Multiple Sclerosis Research, Gottingen, Germany.Division of BioMedical Sciences Faculty of Medicine, Memorial University of Newfoundland, St John's, NL, Canada.Neuroscience Unit, University Hospital Centre of Québec - Laval University, Québec City, QC, Canada.Stem Cell Institute, University of Cambridge, UK.McGill University - Montréal Neurological Institute, Montréal, QC, Canada.McGill University - Montréal Neurological Institute, Montréal, QC, Canada.McGill University - Montréal Neurological Institute, Montréal, QC, Canada.CHUM research centre - Université de Montreal, Montréal, QC, Canada.Division of BioMedical Sciences Faculty of Medicine, Memorial University of Newfoundland, St John's, NL, Canada.McGill University - Montréal Neurological Institute, Montréal, QC, Canada. Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.Neuroscience Unit, University Hospital Centre of Québec - Laval University, Québec City, QC, Canada.CHUM research centre - Université de Montreal, Montréal, QC, Canada.McGill University - Montréal Neurological Institute, Montréal, QC, Canada.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31412103

Citation

Morquette, Barbara, et al. "MicroRNA-223 Protects Neurons From Degeneration in Experimental Autoimmune Encephalomyelitis." Brain : a Journal of Neurology, vol. 142, no. 10, 2019, pp. 2979-2995.
Morquette B, Juźwik CA, Drake SS, et al. MicroRNA-223 protects neurons from degeneration in experimental autoimmune encephalomyelitis. Brain. 2019;142(10):2979-2995.
Morquette, B., Juźwik, C. A., Drake, S. S., Charabati, M., Zhang, Y., Lécuyer, M. A., Galloway, D. A., Dumas, A., de Faria Junior, O., Paradis-Isler, N., Bueno, M., Rambaldi, I., Zandee, S., Moore, C., Bar-Or, A., Vallières, L., Prat, A., & Fournier, A. E. (2019). MicroRNA-223 protects neurons from degeneration in experimental autoimmune encephalomyelitis. Brain : a Journal of Neurology, 142(10), 2979-2995. https://doi.org/10.1093/brain/awz245
Morquette B, et al. MicroRNA-223 Protects Neurons From Degeneration in Experimental Autoimmune Encephalomyelitis. Brain. 2019 10 1;142(10):2979-2995. PubMed PMID: 31412103.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - MicroRNA-223 protects neurons from degeneration in experimental autoimmune encephalomyelitis. AU - Morquette,Barbara, AU - Juźwik,Camille A, AU - Drake,Sienna S, AU - Charabati,Marc, AU - Zhang,Yang, AU - Lécuyer,Marc-André, AU - Galloway,Dylan A, AU - Dumas,Aline, AU - de Faria Junior,Omar, AU - Paradis-Isler,Nicolas, AU - Bueno,Mardja, AU - Rambaldi,Isabel, AU - Zandee,Stephanie, AU - Moore,Craig, AU - Bar-Or,Amit, AU - Vallières,Luc, AU - Prat,Alexandre, AU - Fournier,Alyson E, PY - 2018/11/02/received PY - 2019/05/27/revised PY - 2019/06/19/accepted PY - 2019/8/15/pubmed PY - 2020/6/17/medline PY - 2019/8/15/entrez KW - experimental autoimmune encephalomyelitis KW - glutamate KW - microRNA KW - multiple sclerosis KW - neurodegeneration SP - 2979 EP - 2995 JF - Brain : a journal of neurology JO - Brain VL - 142 IS - 10 N2 - Multiple sclerosis is a chronic inflammatory, demyelinating, and neurodegenerative disease affecting the brain, spinal cord and optic nerves. Neuronal damage is triggered by various harmful factors that engage diverse signalling cascades in neurons; thus, therapeutic approaches to protect neurons will need to focus on agents that can target multiple biological processes. We have therefore focused our attention on microRNAs: small non-coding RNAs that primarily function as post-transcriptional regulators that target messenger RNAs and repress their translation into proteins. A single microRNA can target many functionally related messenger RNAs making microRNAs powerful epigenetic regulators. Dysregulation of microRNAs has been described in many neurodegenerative diseases including multiple sclerosis. Here, we report that two microRNAs, miR-223-3p and miR-27a-3p, are upregulated in neurons in the experimental autoimmune encephalomyelitis mouse model of CNS inflammation and in grey matter-containing multiple sclerosis lesions. Prior work has shown peripheral blood mononuclear cell conditioned media causes sublethal degeneration of neurons in culture. We find overexpression of miR-27a-3p or miR-223-3p protects dissociated cortical neurons from condition media mediated degeneration. Introduction of miR-223-3p in vivo in mouse retinal ganglion cells protects their axons from degeneration in experimental autoimmune encephalomyelitis. In silico analysis revealed that messenger RNAs involved in glutamate receptor signalling are enriched as miR-27a-3p and miR-223-3p targets. We observe that antagonism of NMDA and AMPA type glutamate receptors protects neurons from condition media dependent degeneration. Our results suggest that miR-223-3p and miR-27a-3p are upregulated in response to inflammation to mediate a compensatory neuroprotective gene expression program that desensitizes neurons to glutamate by targeting messenger RNAs involved in glutamate receptor signalling. SN - 1460-2156 UR - https://www.unboundmedicine.com/medline/citation/31412103/MicroRNA_223_protects_neurons_from_degeneration_in_experimental_autoimmune_encephalomyelitis_ DB - PRIME DP - Unbound Medicine ER -