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Neurotoxic potential of reactive astrocytes in canine distemper demyelinating leukoencephalitis
Canine distemper virus (CDV) causes a fatal demyelinating leukoencephalitis in young dogs resembling human multiple sclerosis. Astrocytes are the main cellular target of CDV and undergo reactive changes already in pre-demyelinating brain lesions. Based on their broad range of beneficial and detrimen...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6690900/ https://www.ncbi.nlm.nih.gov/pubmed/31406213 http://dx.doi.org/10.1038/s41598-019-48146-9 |
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author | Klemens, J. Ciurkiewicz, M. Chludzinski, E. Iseringhausen, M. Klotz, D. Pfankuche, V. M. Ulrich, R. Herder, V. Puff, C. Baumgärtner, W. Beineke, A. |
author_facet | Klemens, J. Ciurkiewicz, M. Chludzinski, E. Iseringhausen, M. Klotz, D. Pfankuche, V. M. Ulrich, R. Herder, V. Puff, C. Baumgärtner, W. Beineke, A. |
author_sort | Klemens, J. |
collection | PubMed |
description | Canine distemper virus (CDV) causes a fatal demyelinating leukoencephalitis in young dogs resembling human multiple sclerosis. Astrocytes are the main cellular target of CDV and undergo reactive changes already in pre-demyelinating brain lesions. Based on their broad range of beneficial and detrimental effects in the injured brain reactive astrogliosis is in need of intensive investigation. The aim of the study was to characterize astrocyte plasticity during the course of CDV-induced demyelinating leukoencephalitis by the aid of immunohistochemistry, immunofluorescence and gene expression analysis. Immunohistochemistry revealed the presence of reactive glial fibrillary acidic protein (GFAP)(+) astrocytes with increased survivin and reduced aquaporin 4, and glutamine synthetase protein levels, indicating disturbed blood brain barrier function, glutamate homeostasis and astrocyte maladaptation, respectively. Gene expression analysis revealed 81 differentially expressed astrocyte-related genes with a dominance of genes associated with neurotoxic A1-polarized astrocytes. Accordingly, acyl-coA synthetase long-chain family member 5(+)/GFAP(+), and serglycin(+)/GFAP(+) cells, characteristic of A1-astrocytes, were found in demyelinating lesions by immunofluorescence. In addition, gene expression revealed a dysregulation of astrocytic function including disturbed glutamate homeostasis and altered immune function. Observed findings indicate an astrocyte polarization towards a neurotoxic phenotype likely contributing to lesion initiation and progression in canine distemper leukoencephalitis. |
format | Online Article Text |
id | pubmed-6690900 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-66909002019-08-15 Neurotoxic potential of reactive astrocytes in canine distemper demyelinating leukoencephalitis Klemens, J. Ciurkiewicz, M. Chludzinski, E. Iseringhausen, M. Klotz, D. Pfankuche, V. M. Ulrich, R. Herder, V. Puff, C. Baumgärtner, W. Beineke, A. Sci Rep Article Canine distemper virus (CDV) causes a fatal demyelinating leukoencephalitis in young dogs resembling human multiple sclerosis. Astrocytes are the main cellular target of CDV and undergo reactive changes already in pre-demyelinating brain lesions. Based on their broad range of beneficial and detrimental effects in the injured brain reactive astrogliosis is in need of intensive investigation. The aim of the study was to characterize astrocyte plasticity during the course of CDV-induced demyelinating leukoencephalitis by the aid of immunohistochemistry, immunofluorescence and gene expression analysis. Immunohistochemistry revealed the presence of reactive glial fibrillary acidic protein (GFAP)(+) astrocytes with increased survivin and reduced aquaporin 4, and glutamine synthetase protein levels, indicating disturbed blood brain barrier function, glutamate homeostasis and astrocyte maladaptation, respectively. Gene expression analysis revealed 81 differentially expressed astrocyte-related genes with a dominance of genes associated with neurotoxic A1-polarized astrocytes. Accordingly, acyl-coA synthetase long-chain family member 5(+)/GFAP(+), and serglycin(+)/GFAP(+) cells, characteristic of A1-astrocytes, were found in demyelinating lesions by immunofluorescence. In addition, gene expression revealed a dysregulation of astrocytic function including disturbed glutamate homeostasis and altered immune function. Observed findings indicate an astrocyte polarization towards a neurotoxic phenotype likely contributing to lesion initiation and progression in canine distemper leukoencephalitis. Nature Publishing Group UK 2019-08-12 /pmc/articles/PMC6690900/ /pubmed/31406213 http://dx.doi.org/10.1038/s41598-019-48146-9 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Klemens, J. Ciurkiewicz, M. Chludzinski, E. Iseringhausen, M. Klotz, D. Pfankuche, V. M. Ulrich, R. Herder, V. Puff, C. Baumgärtner, W. Beineke, A. Neurotoxic potential of reactive astrocytes in canine distemper demyelinating leukoencephalitis |
title | Neurotoxic potential of reactive astrocytes in canine distemper demyelinating leukoencephalitis |
title_full | Neurotoxic potential of reactive astrocytes in canine distemper demyelinating leukoencephalitis |
title_fullStr | Neurotoxic potential of reactive astrocytes in canine distemper demyelinating leukoencephalitis |
title_full_unstemmed | Neurotoxic potential of reactive astrocytes in canine distemper demyelinating leukoencephalitis |
title_short | Neurotoxic potential of reactive astrocytes in canine distemper demyelinating leukoencephalitis |
title_sort | neurotoxic potential of reactive astrocytes in canine distemper demyelinating leukoencephalitis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6690900/ https://www.ncbi.nlm.nih.gov/pubmed/31406213 http://dx.doi.org/10.1038/s41598-019-48146-9 |
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