In toxic demyelination oligodendroglial cell death occurs early and is FAS independent
Oligodendroglial cell death is a frequent phenomenon of many neurological diseases, e.g. in demyelinating diseases such as multiple sclerosis (MS). The underlying mechanisms are largely unknown. Here, we demonstrate that in the toxic demyelination cuprizone model, oligodendroglial cell death and dow...
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doaj-dd1058893d8d4e2590de2b6b2ac0bd832021-03-20T04:58:32ZengElsevierNeurobiology of Disease1095-953X2010-02-01372362369In toxic demyelination oligodendroglial cell death occurs early and is FAS independentAmke Hesse0Michael Wagner1Jasmin Held2Wolfgang Brück3Gabriela Salinas-Riester4Zhenyue Hao5Ari Waisman6Tanja Kuhlmann7Institute of Neuropathology, University Hospital Münster, Münster, Domagkstr. 19, 48149 Münster, GermanyDepartment of Neuropathology, University Medical Center Göttingen, GermanyDepartment of Neuropathology, University Medical Center Göttingen, GermanyDepartment of Neuropathology, University Medical Center Göttingen, GermanyDNA Microarray Core Facility, University of Göttingen, GermanyCampell Family Institute for Cancer Research, Ontario Cancer Institute, University Health Network, Toronto, Canada1st Medical Department, Johannes-Gutenberg-University, Mainz, GermanyInstitute of Neuropathology, University Hospital Münster, Münster, Domagkstr. 19, 48149 Münster, Germany; Corresponding author. Fax: +49 251 8356971.Oligodendroglial cell death is a frequent phenomenon of many neurological diseases, e.g. in demyelinating diseases such as multiple sclerosis (MS). The underlying mechanisms are largely unknown. Here, we demonstrate that in the toxic demyelination cuprizone model, oligodendroglial cell death and downregulation of myelin genes start days after initiation of the cuprizone diet and weeks before demyelination is obvious. In early – but not in later – stages, dying oligodendrocytes express activated caspase 3, suggesting a switch from classical apoptotic pathways to caspase 3-independent mechanisms during the course of the cuprizone diet. The expression level of FAS in the corpus callosum, a cell death receptor crucial for oligodendroglial cell death in experimental autoimmune encephalomyelitis (EAE), correlates with the expression of activated caspase 3 in oligodendrocytes. However, mice lacking FAS in oligodendrocytes are not protected against cuprizone-induced oligodendroglial cell death, showing that FAS is dispensable for oligodendroglial cell death in the cuprizone model.http://www.sciencedirect.com/science/article/pii/S0969996109003027MyelinCuprizoneApoptosisFAS |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Amke Hesse Michael Wagner Jasmin Held Wolfgang Brück Gabriela Salinas-Riester Zhenyue Hao Ari Waisman Tanja Kuhlmann |
spellingShingle |
Amke Hesse Michael Wagner Jasmin Held Wolfgang Brück Gabriela Salinas-Riester Zhenyue Hao Ari Waisman Tanja Kuhlmann In toxic demyelination oligodendroglial cell death occurs early and is FAS independent Neurobiology of Disease Myelin Cuprizone Apoptosis FAS |
author_facet |
Amke Hesse Michael Wagner Jasmin Held Wolfgang Brück Gabriela Salinas-Riester Zhenyue Hao Ari Waisman Tanja Kuhlmann |
author_sort |
Amke Hesse |
title |
In toxic demyelination oligodendroglial cell death occurs early and is FAS independent |
title_short |
In toxic demyelination oligodendroglial cell death occurs early and is FAS independent |
title_full |
In toxic demyelination oligodendroglial cell death occurs early and is FAS independent |
title_fullStr |
In toxic demyelination oligodendroglial cell death occurs early and is FAS independent |
title_full_unstemmed |
In toxic demyelination oligodendroglial cell death occurs early and is FAS independent |
title_sort |
in toxic demyelination oligodendroglial cell death occurs early and is fas independent |
publisher |
Elsevier |
series |
Neurobiology of Disease |
issn |
1095-953X |
publishDate |
2010-02-01 |
description |
Oligodendroglial cell death is a frequent phenomenon of many neurological diseases, e.g. in demyelinating diseases such as multiple sclerosis (MS). The underlying mechanisms are largely unknown. Here, we demonstrate that in the toxic demyelination cuprizone model, oligodendroglial cell death and downregulation of myelin genes start days after initiation of the cuprizone diet and weeks before demyelination is obvious. In early – but not in later – stages, dying oligodendrocytes express activated caspase 3, suggesting a switch from classical apoptotic pathways to caspase 3-independent mechanisms during the course of the cuprizone diet. The expression level of FAS in the corpus callosum, a cell death receptor crucial for oligodendroglial cell death in experimental autoimmune encephalomyelitis (EAE), correlates with the expression of activated caspase 3 in oligodendrocytes. However, mice lacking FAS in oligodendrocytes are not protected against cuprizone-induced oligodendroglial cell death, showing that FAS is dispensable for oligodendroglial cell death in the cuprizone model. |
topic |
Myelin Cuprizone Apoptosis FAS |
url |
http://www.sciencedirect.com/science/article/pii/S0969996109003027 |
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