TNF alpha promotes proliferation of oligodendrocyte progenitors and remyelination

Nat Neurosci. 2001 Nov;4(11):1116-22. doi: 10.1038/nn738.


Here we used mice lacking tumor necrosis factor-alpha (TNF alpha) and its associated receptors to study a model of demyelination and remyelination in which these events could be carefully controlled using a toxin, cuprizone. Unexpectedly, the lack of TNF alpha led to a significant delay in remyelination as assessed by histology, immunohistochemistry for myelin proteins and electron microscopy coupled with morphometric analysis. Failure of repair correlated with a reduction in the pool of proliferating oligodendrocyte progenitors (bromodeoxyuridine-labeled NG2(+) cells) followed by a reduction in the number of mature oligodendrocytes. Analysis of mice lacking TNF receptor 1 (TNFR1) or TNFR2 indicated that TNFR2, not TNFR1, is critical to oligodendrocyte regeneration. This unexpected reparative role for TNF alpha in the CNS is important for understanding oligodendrocyte regeneration/proliferation, nerve remyelination and the design of new therapeutics for demyelinating diseases.

Publication types

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

MeSH terms

  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / metabolism*
  • Apoptosis
  • B-Lymphocytes / metabolism
  • Brain Chemistry
  • Corpus Callosum / metabolism
  • Corpus Callosum / ultrastructure
  • Cuprizone / administration & dosage
  • Cuprizone / toxicity
  • Demyelinating Diseases / chemically induced
  • Disease Models, Animal
  • Humans
  • Immunohistochemistry
  • In Situ Nick-End Labeling
  • Macrophages / metabolism
  • Male
  • Mice
  • Mice, Knockout
  • Microglia / metabolism
  • Monoamine Oxidase Inhibitors / pharmacology
  • Myelin Sheath / metabolism*
  • Myelin Sheath / pathology
  • Myelin Sheath / ultrastructure
  • Oligodendroglia / cytology
  • Oligodendroglia / drug effects
  • Oligodendroglia / physiology*
  • Receptors, Tumor Necrosis Factor / genetics
  • Receptors, Tumor Necrosis Factor / metabolism*
  • Receptors, Tumor Necrosis Factor, Type I
  • Receptors, Tumor Necrosis Factor, Type II
  • Stem Cells / physiology*
  • Stem Cells / ultrastructure
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism*
  • Up-Regulation


  • Antigens, CD
  • Monoamine Oxidase Inhibitors
  • Receptors, Tumor Necrosis Factor
  • Receptors, Tumor Necrosis Factor, Type I
  • Receptors, Tumor Necrosis Factor, Type II
  • Tumor Necrosis Factor-alpha
  • Cuprizone