Cargando…

Astrocyte depletion alters extracellular matrix composition in the demyelinating phase of Theiler’s murine encephalomyelitis

Astrocytes produce extracellular matrix (ECM) glycoproteins contributing to the blood-brain barrier and regulating the immune response in the central nervous system (CNS). The aim of this study was to investigate the impact of astrocyte depletion upon the clinical outcome and the composition of ECM...

Descripción completa

Detalles Bibliográficos
Autores principales: Allnoch, Lisa, Leitzen, Eva, Zdora, Isabel, Baumgärtner, Wolfgang, Hansmann, Florian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9205503/
https://www.ncbi.nlm.nih.gov/pubmed/35714111
http://dx.doi.org/10.1371/journal.pone.0270239
_version_ 1784729146935476224
author Allnoch, Lisa
Leitzen, Eva
Zdora, Isabel
Baumgärtner, Wolfgang
Hansmann, Florian
author_facet Allnoch, Lisa
Leitzen, Eva
Zdora, Isabel
Baumgärtner, Wolfgang
Hansmann, Florian
author_sort Allnoch, Lisa
collection PubMed
description Astrocytes produce extracellular matrix (ECM) glycoproteins contributing to the blood-brain barrier and regulating the immune response in the central nervous system (CNS). The aim of this study was to investigate the impact of astrocyte depletion upon the clinical outcome and the composition of ECM glycoproteins in a virus-induced animal model of demyelination. Glial fibrillary acidic protein (GFAP)-thymidine-kinase transgenic SJL (GFAP-knockout) and wildtype mice were infected with Theiler’s murine encephalomyelitis virus (TMEV). Astrocyte depletion was induced during the progressive, demyelinating disease phase by ganciclovir administration once daily between 56 and 77 days post infection (dpi). At 77 dpi GFAP-knockout mice showed a significant deterioration of clinical signs associated with a reduction of azan and picrosirius red stained ECM-molecules in the thoracic spinal cord. Basement-membrane-associated ECM-molecules including laminin, entactin/nidogen-1 and Kir4.1 as well as non-basement membrane-associated ECM-molecules like collagen I, decorin, tenascin-R and CD44 were significantly reduced in the spinal cord of GFAP-knockout mice. The reduction of the investigated ECM-molecules demonstrates that astrocytes play a key role in the production of ECM-molecules. The present findings indicate that the detected loss of Kir4.1 and CD44 as well as the disruption of the integrity of perineuronal nets led to the deterioration of clinical signs in GFAP-knockout mice.
format Online
Article
Text
id pubmed-9205503
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-92055032022-06-18 Astrocyte depletion alters extracellular matrix composition in the demyelinating phase of Theiler’s murine encephalomyelitis Allnoch, Lisa Leitzen, Eva Zdora, Isabel Baumgärtner, Wolfgang Hansmann, Florian PLoS One Research Article Astrocytes produce extracellular matrix (ECM) glycoproteins contributing to the blood-brain barrier and regulating the immune response in the central nervous system (CNS). The aim of this study was to investigate the impact of astrocyte depletion upon the clinical outcome and the composition of ECM glycoproteins in a virus-induced animal model of demyelination. Glial fibrillary acidic protein (GFAP)-thymidine-kinase transgenic SJL (GFAP-knockout) and wildtype mice were infected with Theiler’s murine encephalomyelitis virus (TMEV). Astrocyte depletion was induced during the progressive, demyelinating disease phase by ganciclovir administration once daily between 56 and 77 days post infection (dpi). At 77 dpi GFAP-knockout mice showed a significant deterioration of clinical signs associated with a reduction of azan and picrosirius red stained ECM-molecules in the thoracic spinal cord. Basement-membrane-associated ECM-molecules including laminin, entactin/nidogen-1 and Kir4.1 as well as non-basement membrane-associated ECM-molecules like collagen I, decorin, tenascin-R and CD44 were significantly reduced in the spinal cord of GFAP-knockout mice. The reduction of the investigated ECM-molecules demonstrates that astrocytes play a key role in the production of ECM-molecules. The present findings indicate that the detected loss of Kir4.1 and CD44 as well as the disruption of the integrity of perineuronal nets led to the deterioration of clinical signs in GFAP-knockout mice. Public Library of Science 2022-06-17 /pmc/articles/PMC9205503/ /pubmed/35714111 http://dx.doi.org/10.1371/journal.pone.0270239 Text en © 2022 Allnoch et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://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
Allnoch, Lisa
Leitzen, Eva
Zdora, Isabel
Baumgärtner, Wolfgang
Hansmann, Florian
Astrocyte depletion alters extracellular matrix composition in the demyelinating phase of Theiler’s murine encephalomyelitis
title Astrocyte depletion alters extracellular matrix composition in the demyelinating phase of Theiler’s murine encephalomyelitis
title_full Astrocyte depletion alters extracellular matrix composition in the demyelinating phase of Theiler’s murine encephalomyelitis
title_fullStr Astrocyte depletion alters extracellular matrix composition in the demyelinating phase of Theiler’s murine encephalomyelitis
title_full_unstemmed Astrocyte depletion alters extracellular matrix composition in the demyelinating phase of Theiler’s murine encephalomyelitis
title_short Astrocyte depletion alters extracellular matrix composition in the demyelinating phase of Theiler’s murine encephalomyelitis
title_sort astrocyte depletion alters extracellular matrix composition in the demyelinating phase of theiler’s murine encephalomyelitis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9205503/
https://www.ncbi.nlm.nih.gov/pubmed/35714111
http://dx.doi.org/10.1371/journal.pone.0270239
work_keys_str_mv AT allnochlisa astrocytedepletionaltersextracellularmatrixcompositioninthedemyelinatingphaseoftheilersmurineencephalomyelitis
AT leitzeneva astrocytedepletionaltersextracellularmatrixcompositioninthedemyelinatingphaseoftheilersmurineencephalomyelitis
AT zdoraisabel astrocytedepletionaltersextracellularmatrixcompositioninthedemyelinatingphaseoftheilersmurineencephalomyelitis
AT baumgartnerwolfgang astrocytedepletionaltersextracellularmatrixcompositioninthedemyelinatingphaseoftheilersmurineencephalomyelitis
AT hansmannflorian astrocytedepletionaltersextracellularmatrixcompositioninthedemyelinatingphaseoftheilersmurineencephalomyelitis