IFNgamma enhances microglial reactions to hippocampal axonal degeneration.

M B Jensen, I V Hegelund, N D Lomholt, B Finsen, T Owens

Research output: Contribution to journalJournal articleResearchpeer-review


Glial reactivity is implicated in CNS repair and regenerative responses. Microglia, the cells responding earliest to axonal injury, produce tumor necrosis factor-alpha (TNFalpha), a cytokine with both cytopathic and neuroprotective effects. We have studied activation of hippocampal microglia to produce TNFalpha in response to transection of perforant path axons in SJL/J mice. TNFalpha mRNA was produced in a transient manner, peaking at 2 d and falling again by 5 d after lesioning. This was unlike other markers of glial reactivity, such as Mac-1 upregulation, which were sustained over longer time periods. Message for the immune cytokine interferon-gamma (IFNgamma) was undetectable, and glial reactivity to axonal lesions occurred as normal in IFNgamma-deficient mice. Microglial responses to lesion-induced neuronal injury were markedly enhanced in myelin basic protein promoter-driven transgenic mice, in which IFNgamma was endogenously produced in hippocampus. The kinetics of TNFalpha downregulation 5 d after lesion was not affected by transgenic IFNgamma, indicating that IFNgamma acts as an amplifier and not an inducer of response. These results are discussed in the context of a regenerative role for TNFalpha in the CNS, which is innately regulated and potentiated by IFNgamma.
Original languageEnglish
JournalJournal of Neuroscience
Issue number10
Pages (from-to)3612-21
Number of pages9
Publication statusPublished - 15. May 2000


  • Animals
  • Antineoplastic Agents
  • Axons
  • Denervation
  • Gene Expression
  • Hippocampus
  • In Situ Hybridization
  • Interferon Type II
  • Macrophage-1 Antigen
  • Mice
  • Mice, Transgenic
  • Microglia
  • Myelin Basic Proteins
  • Nerve Degeneration
  • Oligodendroglia
  • Perforant Pathway
  • RNA, Messenger
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Necrosis Factor-alpha


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