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The Journal of Neuroscience, May 15, 2000, 20(10):3612-3621
IFN Enhances Microglial Reactions to Hippocampal Axonal
Degeneration
Michael B.
Jensen1, 2,
Iørn V.
Hegelund1,
Nina D.
Lomholt1, 2,
Bente
Finsen1, and
Trevor
Owens2
1 Department of Anatomy and Neurobiology, University of
Southern Denmark/Odense University, Odense C, DK 5000 Denmark, and
2 Montreal Neurological Institute, McGill University,
Montreal, Quebec, Canada H3A 2B4
Glial reactivity is implicated in CNS repair and regenerative
responses. Microglia, the cells responding earliest to axonal injury,
produce tumor necrosis factor- (TNF), a cytokine with both
cytopathic and neuroprotective effects. We have studied activation of
hippocampal microglia to produce TNF in response to transection of
perforant path axons in SJL/J mice. TNF 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- (IFN) was undetectable, and glial reactivity to axonal lesions occurred as normal
in IFN-deficient mice. Microglial responses to lesion-induced neuronal injury were markedly enhanced in myelin basic protein promoter-driven transgenic mice, in which IFN was endogenously produced in hippocampus. The kinetics of TNF downregulation 5 d
after lesion was not affected by transgenic IFN, indicating that
IFN acts as an amplifier and not an inducer of response. These
results are discussed in the context of a regenerative role for TNF
in the CNS, which is innately regulated and potentiated by IFN.
Key words:
fascia dentata; axonal lesioning; microglia; tumor
necrosis factor-; transgenic mice; oligodendrocytes
Copyright © 2000 Society for Neuroscience 0270-6474/00/20103612-10$05.00/0
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