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 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.
Institute of Neuropathology, University Hospital Münster, Münster, Germany.
Amke
A
Hesse
Michael
M
Wagner
Jasmin
J
Held
Wolfgang
W
Brück
Gabriela
G
Salinas-Riester
Zhenyue
Z
Hao
Ari
A
Waisman
Tanja
T
Kuhlmann
D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D003337:Corpus Callosum / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D003471:Cuprizone / Q000633:toxicity; D003603:Cytotoxins / Q000633:toxicity; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009185:Myelin Proteins / Q000235:genetics; D009413:Nerve Fibers, Myelinated / Q000378:metabolism* / Q000473:pathology; D009836:Oligodendroglia / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D019014:fas Receptor / Q000378:metabolism*
D003603:Cytotoxins; D009185:Myelin Proteins; D012333:RNA, Messenger; D019014:fas Receptor; D003471:Cuprizone; D053148:Caspase 3