Astrocytes produce CNTF during the remyelination phase of viral-induced spinal cord demyelination to stimulate FGF-2 production

Neurobiol Dis. 2003 Jul;13(2):89-101. doi: 10.1016/s0969-9961(03)00019-6.

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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenergic Uptake Inhibitors / metabolism
  • Animals
  • Astrocytes / metabolism*
  • Cell Culture Techniques
  • Ciliary Neurotrophic Factor / genetics
  • Ciliary Neurotrophic Factor / metabolism*
  • Demyelinating Diseases / metabolism*
  • Female
  • Fibroblast Growth Factor 2 / genetics
  • Fibroblast Growth Factor 2 / metabolism*
  • Fibroblast Growth Factor 9
  • Fibroblast Growth Factors / metabolism
  • Immunohistochemistry
  • In Situ Hybridization
  • Interleukin-1 / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • Receptor, Fibroblast Growth Factor, Type 1
  • Receptor, Fibroblast Growth Factor, Type 2
  • Receptors, Fibroblast Growth Factor / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Spinal Cord / metabolism*
  • Sympathomimetics / metabolism
  • Time Factors
  • Tyramine / metabolism

Substances

  • Adrenergic Uptake Inhibitors
  • Ciliary Neurotrophic Factor
  • Fgf9 protein, mouse
  • Fgf9 protein, rat
  • Fibroblast Growth Factor 9
  • Interleukin-1
  • RNA, Messenger
  • Receptors, Fibroblast Growth Factor
  • Sympathomimetics
  • Fibroblast Growth Factor 2
  • Fibroblast Growth Factors
  • Fgfr1 protein, mouse
  • Fgfr1 protein, rat
  • Fgfr2 protein, mouse
  • Fgfr2 protein, rat
  • Receptor Protein-Tyrosine Kinases
  • Receptor, Fibroblast Growth Factor, Type 1
  • Receptor, Fibroblast Growth Factor, Type 2
  • Tyramine