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Proteomic changes during experimental de- and remyelination in the corpus callosum

BACKGROUND: In the cuprizone model of multiple sclerosis, de- and remyelination can be studied without major interference from the adaptive immune responses. Since previous proteomic studies did not focus on the corpus callosum, where cuprizone causes the most pronounced demyelination, we performed...

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Autores principales: Szilagyi, Gabor T., Nawrocki, Arkadiusz M., Eros, Krisztian, Schmidt, Janos, Fekete, Katalin, Elkjaer, Maria L., Hyrlov, Kirsten H., Larsen, Martin R., Illes, Zsolt, Gallyas, Ferenc
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7145428/
https://www.ncbi.nlm.nih.gov/pubmed/32272486
http://dx.doi.org/10.1371/journal.pone.0230249
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author Szilagyi, Gabor T.
Nawrocki, Arkadiusz M.
Eros, Krisztian
Schmidt, Janos
Fekete, Katalin
Elkjaer, Maria L.
Hyrlov, Kirsten H.
Larsen, Martin R.
Illes, Zsolt
Gallyas, Ferenc
author_facet Szilagyi, Gabor T.
Nawrocki, Arkadiusz M.
Eros, Krisztian
Schmidt, Janos
Fekete, Katalin
Elkjaer, Maria L.
Hyrlov, Kirsten H.
Larsen, Martin R.
Illes, Zsolt
Gallyas, Ferenc
author_sort Szilagyi, Gabor T.
collection PubMed
description BACKGROUND: In the cuprizone model of multiple sclerosis, de- and remyelination can be studied without major interference from the adaptive immune responses. Since previous proteomic studies did not focus on the corpus callosum, where cuprizone causes the most pronounced demyelination, we performed a bottom up proteomic analysis on this brain region. METHODS: Eight week-old mice treated with 0.2% cuprizone, for 4 weeks and controls (C) were sacrificed after termination of the treatment (4wD), and 2 (2dR) or 14 (2wR) days later. Homogenates of dissected corpus callosum were analysed by quantitative proteomics. For data processing, clustering, gene ontology analysis, and regulatory network prediction, we used Perseus, PANTHER and Ingenuity Pathway Analysis softwares, respectively. RESULTS: We identified 4886 unmodified, single- or multi phosphorylated and/or gycosylated (PTM) proteins. Out of them, 191 proteins were differentially regulated in at least one experimental group. We found 57 proteins specific for demyelination, 27 for early- and 57 for late remyelinationwhile 36 proteins were affected in two, and 23 proteins in all three groups. Phosphorylation represented 92% of the post translational modifications among differentially regulated modified (PTM) proteins with decreased level, while it was only 30% of the PTM proteins with increased level. Gene ontology analysis could not classify the demyelination specific proteins into any biological process category, while allocated the remyelination specific ones to nervous system development and myelination as the most specific subcategory. We also identified a protein network in experimental remyelination, and the gene orthologues of the network were differentially expressed in remyelinating multiple sclerosis brain lesions consistent with an early remyelination pattern. CONCLUSION: Proteomic analysis seems more informative for remyelination than demyelination in the cuprizone model.
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spelling pubmed-71454282020-04-14 Proteomic changes during experimental de- and remyelination in the corpus callosum Szilagyi, Gabor T. Nawrocki, Arkadiusz M. Eros, Krisztian Schmidt, Janos Fekete, Katalin Elkjaer, Maria L. Hyrlov, Kirsten H. Larsen, Martin R. Illes, Zsolt Gallyas, Ferenc PLoS One Research Article BACKGROUND: In the cuprizone model of multiple sclerosis, de- and remyelination can be studied without major interference from the adaptive immune responses. Since previous proteomic studies did not focus on the corpus callosum, where cuprizone causes the most pronounced demyelination, we performed a bottom up proteomic analysis on this brain region. METHODS: Eight week-old mice treated with 0.2% cuprizone, for 4 weeks and controls (C) were sacrificed after termination of the treatment (4wD), and 2 (2dR) or 14 (2wR) days later. Homogenates of dissected corpus callosum were analysed by quantitative proteomics. For data processing, clustering, gene ontology analysis, and regulatory network prediction, we used Perseus, PANTHER and Ingenuity Pathway Analysis softwares, respectively. RESULTS: We identified 4886 unmodified, single- or multi phosphorylated and/or gycosylated (PTM) proteins. Out of them, 191 proteins were differentially regulated in at least one experimental group. We found 57 proteins specific for demyelination, 27 for early- and 57 for late remyelinationwhile 36 proteins were affected in two, and 23 proteins in all three groups. Phosphorylation represented 92% of the post translational modifications among differentially regulated modified (PTM) proteins with decreased level, while it was only 30% of the PTM proteins with increased level. Gene ontology analysis could not classify the demyelination specific proteins into any biological process category, while allocated the remyelination specific ones to nervous system development and myelination as the most specific subcategory. We also identified a protein network in experimental remyelination, and the gene orthologues of the network were differentially expressed in remyelinating multiple sclerosis brain lesions consistent with an early remyelination pattern. CONCLUSION: Proteomic analysis seems more informative for remyelination than demyelination in the cuprizone model. Public Library of Science 2020-04-09 /pmc/articles/PMC7145428/ /pubmed/32272486 http://dx.doi.org/10.1371/journal.pone.0230249 Text en © 2020 Szilagyi et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Szilagyi, Gabor T.
Nawrocki, Arkadiusz M.
Eros, Krisztian
Schmidt, Janos
Fekete, Katalin
Elkjaer, Maria L.
Hyrlov, Kirsten H.
Larsen, Martin R.
Illes, Zsolt
Gallyas, Ferenc
Proteomic changes during experimental de- and remyelination in the corpus callosum
title Proteomic changes during experimental de- and remyelination in the corpus callosum
title_full Proteomic changes during experimental de- and remyelination in the corpus callosum
title_fullStr Proteomic changes during experimental de- and remyelination in the corpus callosum
title_full_unstemmed Proteomic changes during experimental de- and remyelination in the corpus callosum
title_short Proteomic changes during experimental de- and remyelination in the corpus callosum
title_sort proteomic changes during experimental de- and remyelination in the corpus callosum
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7145428/
https://www.ncbi.nlm.nih.gov/pubmed/32272486
http://dx.doi.org/10.1371/journal.pone.0230249
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