Abstract
Inflammatory cytokines have been implicated in the pathology of multiple neurologic diseases, including multiple sclerosis. We examined the role of the TNF family member TWEAK in neuroinflammation. Cuprizone-fed mice undergo neuroinflammation and demyelination in the brain, but upon removal of cuprizone from the diet, inflammation is resolved and remyelination occurs. Using this model, we demonstrate that mice lacking TWEAK exhibit a significant delay in demyelination and microglial infiltration. During remyelination, mice lacking the TWEAK gene demonstrate only a marginal delay in remyelination. Thus, this study identifies a primary role of TWEAK in promoting neuroinflammation and exacerbating demyelination during cuprizone-induced damage.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Astrocytes / metabolism
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Astrocytes / pathology
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Chelating Agents / toxicity
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Copper
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Cuprizone / toxicity
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Cytokine TWEAK
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Demyelinating Diseases / chemically induced
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Demyelinating Diseases / physiopathology*
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Double-Blind Method
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Encephalitis / chemically induced
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Encephalitis / physiopathology*
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Microglia / metabolism
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Microglia / pathology
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Myelin Sheath / physiology
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Oligodendroglia / metabolism
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Oligodendroglia / pathology
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RNA, Messenger / biosynthesis
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Receptors, Tumor Necrosis Factor / physiology
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TWEAK Receptor
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Tumor Necrosis Factors / biosynthesis
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Tumor Necrosis Factors / deficiency
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Tumor Necrosis Factors / genetics
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Tumor Necrosis Factors / physiology*
Substances
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Chelating Agents
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Cytokine TWEAK
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RNA, Messenger
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Receptors, Tumor Necrosis Factor
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TWEAK Receptor
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Tnfsf12 protein, mouse
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Tumor Necrosis Factors
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Cuprizone
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Copper