TY - JOUR T1 - IFNγ Enhances Microglial Reactions to Hippocampal Axonal Degeneration JF - The Journal of Neuroscience JO - J. Neurosci. SP - 3612 LP - 3621 DO - 10.1523/JNEUROSCI.20-10-03612.2000 VL - 20 IS - 10 AU - Michael B. Jensen AU - Iørn V. Hegelund AU - Nina D. Lomholt AU - Bente Finsen AU - Trevor Owens Y1 - 2000/05/15 UR - http://www.jneurosci.org/content/20/10/3612.abstract N2 - Glial reactivity is implicated in CNS repair and regenerative responses. Microglia, the cells responding earliest to axonal injury, produce tumor necrosis factor-α (TNFα), a cytokine with both cytopathic and neuroprotective effects. We have studied activation of hippocampal microglia to produce TNFα in response to transection of perforant path axons in SJL/J mice. TNFα 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-γ (IFNγ) was undetectable, and glial reactivity to axonal lesions occurred as normal in IFNγ-deficient mice. Microglial responses to lesion-induced neuronal injury were markedly enhanced in myelin basic protein promoter-driven transgenic mice, in which IFNγ was endogenously produced in hippocampus. The kinetics of TNFα downregulation 5 d after lesion was not affected by transgenic IFNγ, indicating that IFNγ acts as an amplifier and not an inducer of response. These results are discussed in the context of a regenerative role for TNFα in the CNS, which is innately regulated and potentiated by IFNγ. ER -