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Cortical Pathology in Vanishing White Matter
Vanishing white matter (VWM) is classified as a leukodystrophy with astrocytes as primary drivers in its pathogenesis. Magnetic resonance imaging has documented the progressive thinning of cortices in long-surviving patients. Routine histopathological analyses, however, have not yet pointed to corti...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9688115/ https://www.ncbi.nlm.nih.gov/pubmed/36429009 http://dx.doi.org/10.3390/cells11223581 |
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author | Man, Jodie H. K. van Gelder, Charlotte A. G. H. Breur, Marjolein Okkes, Daniel Molenaar, Douwe van der Sluis, Sophie Abbink, Truus Altelaar, Maarten van der Knaap, Marjo S. Bugiani, Marianna |
author_facet | Man, Jodie H. K. van Gelder, Charlotte A. G. H. Breur, Marjolein Okkes, Daniel Molenaar, Douwe van der Sluis, Sophie Abbink, Truus Altelaar, Maarten van der Knaap, Marjo S. Bugiani, Marianna |
author_sort | Man, Jodie H. K. |
collection | PubMed |
description | Vanishing white matter (VWM) is classified as a leukodystrophy with astrocytes as primary drivers in its pathogenesis. Magnetic resonance imaging has documented the progressive thinning of cortices in long-surviving patients. Routine histopathological analyses, however, have not yet pointed to cortical involvement in VWM. Here, we provide a comprehensive analysis of the VWM cortex. We employed high-resolution-mass-spectrometry-based proteomics and immunohistochemistry to gain insight into possible molecular disease mechanisms in the cortices of VWM patients. The proteome analysis revealed 268 differentially expressed proteins in the VWM cortices compared to the controls. A majority of these proteins formed a major protein interaction network. A subsequent gene ontology analysis identified enrichment for terms such as cellular metabolism, particularly mitochondrial activity. Importantly, some of the proteins with the most prominent changes in expression were found in astrocytes, indicating cortical astrocytic involvement. Indeed, we confirmed that VWM cortical astrocytes exhibit morphological changes and are less complex in structure than control cells. Our findings also suggest that these astrocytes are immature and not reactive. Taken together, we provide insights into cortical involvement in VWM, which has to be taken into account when developing therapeutic strategies. |
format | Online Article Text |
id | pubmed-9688115 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-96881152022-11-25 Cortical Pathology in Vanishing White Matter Man, Jodie H. K. van Gelder, Charlotte A. G. H. Breur, Marjolein Okkes, Daniel Molenaar, Douwe van der Sluis, Sophie Abbink, Truus Altelaar, Maarten van der Knaap, Marjo S. Bugiani, Marianna Cells Article Vanishing white matter (VWM) is classified as a leukodystrophy with astrocytes as primary drivers in its pathogenesis. Magnetic resonance imaging has documented the progressive thinning of cortices in long-surviving patients. Routine histopathological analyses, however, have not yet pointed to cortical involvement in VWM. Here, we provide a comprehensive analysis of the VWM cortex. We employed high-resolution-mass-spectrometry-based proteomics and immunohistochemistry to gain insight into possible molecular disease mechanisms in the cortices of VWM patients. The proteome analysis revealed 268 differentially expressed proteins in the VWM cortices compared to the controls. A majority of these proteins formed a major protein interaction network. A subsequent gene ontology analysis identified enrichment for terms such as cellular metabolism, particularly mitochondrial activity. Importantly, some of the proteins with the most prominent changes in expression were found in astrocytes, indicating cortical astrocytic involvement. Indeed, we confirmed that VWM cortical astrocytes exhibit morphological changes and are less complex in structure than control cells. Our findings also suggest that these astrocytes are immature and not reactive. Taken together, we provide insights into cortical involvement in VWM, which has to be taken into account when developing therapeutic strategies. MDPI 2022-11-12 /pmc/articles/PMC9688115/ /pubmed/36429009 http://dx.doi.org/10.3390/cells11223581 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Man, Jodie H. K. van Gelder, Charlotte A. G. H. Breur, Marjolein Okkes, Daniel Molenaar, Douwe van der Sluis, Sophie Abbink, Truus Altelaar, Maarten van der Knaap, Marjo S. Bugiani, Marianna Cortical Pathology in Vanishing White Matter |
title | Cortical Pathology in Vanishing White Matter |
title_full | Cortical Pathology in Vanishing White Matter |
title_fullStr | Cortical Pathology in Vanishing White Matter |
title_full_unstemmed | Cortical Pathology in Vanishing White Matter |
title_short | Cortical Pathology in Vanishing White Matter |
title_sort | cortical pathology in vanishing white matter |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9688115/ https://www.ncbi.nlm.nih.gov/pubmed/36429009 http://dx.doi.org/10.3390/cells11223581 |
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