Abstract
Fibroblast growth factor-2 (FGF-2) controls in part the timely differentiation of oligodendrocytes into the myelin-producing cells of the CNS. However, although differentiated oligodendrocytes express FGF receptors (R), the effect of FGF-2 on myelin-producing oligodendrocytes in vivo was unknown. In the present study, we show that delivery of FGF-2 into the cerebrospinal fluid of anaesthetized rat pups, aged postnatal day (P) 6 to 9, induced a severe loss of myelin in the caudal anterior medullary velum (AMV). Furthermore, we show that the caudal AMV was myelinated at the time of treatment, so the effects of FGF-2 represent a loss of myelin and not delayed differentiation. This was confirmed by injection of platelet-derived growth factor-AA (PDGF-AA), a factor known to affect the differentiation of PDGF-alphaR expressing oligodendrocyte progenitors, but which did not induce myelin loss in the caudal AMV and did not affect differentiated oligodendrocytes, which do not express PDGF-alphaR. Compared to controls treated with saline or PDGF-AA, FGF-2 induced an accumulation of PLP protein and MBP mRNA within the somata of myelin-producing oligodendrocytes. The results indicate that FGF receptor signalling disrupts myelin production in differentiated oligodendrocytes in vivo and interrupted the transport of myelin-related gene products from the oligodendrocyte cell body to their myelin sheaths.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Brain / drug effects
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Brain / growth & development*
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Brain / metabolism
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Cell Death / drug effects
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Cell Death / physiology
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Cell Differentiation / drug effects
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Cell Differentiation / physiology*
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Demyelinating Diseases / metabolism
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Demyelinating Diseases / pathology
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Demyelinating Diseases / physiopathology
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Female
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Fibroblast Growth Factor 2 / metabolism*
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Fibroblast Growth Factor 2 / pharmacology
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Growth Inhibitors / metabolism*
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Growth Inhibitors / pharmacology
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Male
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Myelin Proteins / biosynthesis
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Myelin Proteins / drug effects
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Myelin Proteins / genetics
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Myelin Sheath / metabolism*
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Nerve Fibers, Myelinated / drug effects
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Nerve Fibers, Myelinated / metabolism
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Nerve Fibers, Myelinated / ultrastructure
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Oligodendroglia / drug effects
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Oligodendroglia / metabolism*
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Oligodendroglia / pathology
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Platelet-Derived Growth Factor / metabolism
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Platelet-Derived Growth Factor / pharmacology
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RNA, Messenger / drug effects
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RNA, Messenger / metabolism
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Rats
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Rats, Wistar
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Receptors, Fibroblast Growth Factor / drug effects
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Receptors, Fibroblast Growth Factor / metabolism*
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Signal Transduction / drug effects
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Signal Transduction / physiology
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Wallerian Degeneration / chemically induced
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Wallerian Degeneration / pathology
Substances
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Growth Inhibitors
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Myelin Proteins
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Platelet-Derived Growth Factor
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RNA, Messenger
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Receptors, Fibroblast Growth Factor
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platelet-derived growth factor A
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Fibroblast Growth Factor 2