Fibroblast growth factor 2 induces loss of adult oligodendrocytes and myelin in vivo

Exp Neurol. 2005 Mar;192(1):125-33. doi: 10.1016/j.expneurol.2004.11.007.

Abstract

Oligodendrocytes are the myelin-forming cells of the CNS and are lost in demyelinating diseases such as multiple sclerosis (MS). A role for fibroblast growth factor 2 (FGF2) has been proposed in the pathogenesis of demyelination and the failure of remyelination in experimental models of MS. However, the in vivo effects of FGF2 on oligodendrocytes and oligodendrocyte progenitors (OPCs) in the adult CNS had not previously been determined. To address this, FGF2 was delivered into the cerebrospinal fluid (CSF) of the IVth ventricle and its actions were examined on the anterior medullary velum (AMV), a thin tissue that partly roofs the IVth ventricle and is bathed by CSF. FGF2 was administered twice daily for 3 days and AMV were analysed using immunohistochemical labelling; saline was administered in controls. The results show that raised FGF2 induces severe disruption of mature oligodendrocytes and a marked loss of myelin. At the same time, FGF2 treatment resulted in the aberrant accumulation of immature oligodendrocytes with a premyelinating phenotype, together with NG2-expressing OPCs. Axons are patent within demyelinated lesions, and they are contacted but not ensheathed by surviving oligodendrocytes, newly formed premyelinating oligodendrocytes and OPCs. These results demonstrate that raised FGF2 induces demyelination in the adult CNS, and support a role for FGF2 in the pathogenesis of demyelination and regulation of remyelination in MS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens / metabolism
  • Cell Death / drug effects
  • Cell Death / physiology
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology
  • Disease Models, Animal
  • Female
  • Fibroblast Growth Factor 2 / pharmacology*
  • Fourth Ventricle / cytology
  • Fourth Ventricle / drug effects
  • Fourth Ventricle / metabolism
  • Injections, Intraventricular
  • Male
  • Multiple Sclerosis / chemically induced
  • Multiple Sclerosis / metabolism*
  • Multiple Sclerosis / physiopathology
  • Myelin Sheath / drug effects
  • Myelin Sheath / metabolism*
  • Myelin Sheath / pathology
  • Nerve Fibers, Myelinated / drug effects
  • Nerve Fibers, Myelinated / metabolism*
  • Nerve Fibers, Myelinated / pathology
  • Nerve Regeneration / drug effects
  • Nerve Regeneration / physiology*
  • Oligodendroglia / drug effects
  • Oligodendroglia / metabolism*
  • Oligodendroglia / pathology
  • Proteoglycans / metabolism
  • Rats
  • Rats, Wistar
  • Stem Cells / drug effects
  • Stem Cells / metabolism

Substances

  • Antigens
  • Proteoglycans
  • chondroitin sulfate proteoglycan 4
  • Fibroblast Growth Factor 2