Abstract
Multiple sclerosis is characterized by multiple lesions with selective loss of myelin and oligodendrocytes, leading to deficits of sensation and movement, as well as cognitive disabilities. Consequently, a major research endeavor is to identify strategies to enhance oligodendrocyte regeneration and remyelination. FGF-2 is a potent mitogen for OPCs, and it is induced in astrocytes in animal models of demyelinating diseases in conjunction with successful remyelination. However, the factors responsible for inducing FGF-2 after demyelination in astrocytes are unknown. Here we show that CNTF mRNA and protein increase coincident with spinal cord remyelination in mice recovering from MHV-induced demyelination. We identify CNTF within astrocytes surrounding and within remyelinating lesions, and show that CNTF increases FGF-2 ligand and receptor mRNAs in spinal cord after direct application. Furthermore, we show that CNTF increases FGF-2 mRNA approximately 2.5-fold in cultured mouse spinal cord astrocytes. Altogether, these results strongly implicate CNTF as an important cytokine in demyelinating disease and as an upstream regulator of FGF-2 production in astrocytes during early remyelination.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adrenergic Uptake Inhibitors / metabolism
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Animals
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Astrocytes / metabolism*
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Cell Culture Techniques
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Ciliary Neurotrophic Factor / genetics
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Ciliary Neurotrophic Factor / metabolism*
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Demyelinating Diseases / metabolism*
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Female
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Fibroblast Growth Factor 2 / genetics
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Fibroblast Growth Factor 2 / metabolism*
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Fibroblast Growth Factor 9
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Fibroblast Growth Factors / metabolism
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Immunohistochemistry
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In Situ Hybridization
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Interleukin-1 / metabolism
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Male
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Mice
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Mice, Inbred C57BL
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RNA, Messenger / metabolism
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Rats
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Rats, Sprague-Dawley
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Receptor Protein-Tyrosine Kinases / metabolism*
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Receptor, Fibroblast Growth Factor, Type 1
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Receptor, Fibroblast Growth Factor, Type 2
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Receptors, Fibroblast Growth Factor / metabolism*
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Reverse Transcriptase Polymerase Chain Reaction
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Spinal Cord / metabolism*
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Sympathomimetics / metabolism
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Time Factors
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Tyramine / metabolism
Substances
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Adrenergic Uptake Inhibitors
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Ciliary Neurotrophic Factor
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Fgf9 protein, mouse
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Fgf9 protein, rat
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Fibroblast Growth Factor 9
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Interleukin-1
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RNA, Messenger
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Receptors, Fibroblast Growth Factor
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Sympathomimetics
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Fibroblast Growth Factor 2
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Fibroblast Growth Factors
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Fgfr1 protein, mouse
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Fgfr1 protein, rat
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Fgfr2 protein, mouse
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Fgfr2 protein, rat
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Receptor Protein-Tyrosine Kinases
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Receptor, Fibroblast Growth Factor, Type 1
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Receptor, Fibroblast Growth Factor, Type 2
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Tyramine