Fibroblast growth factor-2 inhibits myelin production by oligodendrocytes in vivo

Mol Cell Neurosci. 2001 Nov;18(5):557-69. doi: 10.1006/mcne.2001.1025.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / drug effects
  • Brain / growth & development*
  • Brain / metabolism
  • Cell Death / drug effects
  • Cell Death / physiology
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology*
  • Demyelinating Diseases / metabolism
  • Demyelinating Diseases / pathology
  • Demyelinating Diseases / physiopathology
  • Female
  • Fibroblast Growth Factor 2 / metabolism*
  • Fibroblast Growth Factor 2 / pharmacology
  • Growth Inhibitors / metabolism*
  • Growth Inhibitors / pharmacology
  • Male
  • Myelin Proteins / biosynthesis
  • Myelin Proteins / drug effects
  • Myelin Proteins / genetics
  • Myelin Sheath / metabolism*
  • Nerve Fibers, Myelinated / drug effects
  • Nerve Fibers, Myelinated / metabolism
  • Nerve Fibers, Myelinated / ultrastructure
  • Oligodendroglia / drug effects
  • Oligodendroglia / metabolism*
  • Oligodendroglia / pathology
  • Platelet-Derived Growth Factor / metabolism
  • Platelet-Derived Growth Factor / pharmacology
  • RNA, Messenger / drug effects
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Receptors, Fibroblast Growth Factor / drug effects
  • Receptors, Fibroblast Growth Factor / metabolism*
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Wallerian Degeneration / chemically induced
  • Wallerian Degeneration / pathology

Substances

  • Growth Inhibitors
  • Myelin Proteins
  • Platelet-Derived Growth Factor
  • RNA, Messenger
  • Receptors, Fibroblast Growth Factor
  • platelet-derived growth factor A
  • Fibroblast Growth Factor 2