In toxic demyelination oligodendroglial cell death occurs early and is FAS independent

NEUROBIOLOGY OF DISEASE

卷:37

Article

Hesse, Amke¹  Wagner, Michael²  Held, Jasmin²  Brikk, Wolfgang²  Salinas-Riester, Gabriela³  Hao, Zhenyue⁴  Waisman, Ari⁵  Kuhlmann, Tanja¹ 

[1] Univ Hosp Munster, Inst Neuropathol, D-48149 Munster, Germany

[2] Univ Med Ctr Gottingen, Dept Neuropathol, Gottingen, Germany

[3] Univ Gottingen, DNA Microarray Core Facil, D-3400 Gottingen, Germany

[4] Univ Hlth Network, Ontario Canc Inst, Campell Family Inst Canc Res, Toronto, ON, Canada

[5] Johannes Gutenberg Univ Mainz, Dept Med 1, D-6500 Mainz, Germany

关键词: Myelin;    Cuprizone;    Apoptosis;    FAS;   

DOI  :  10.1016/j.nbd.2009.10.016

来源: Elsevier

【 摘 要 】

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. (c) 2009 Elsevier Inc. All rights reserved.

【 授权许可】

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