@article{889b5dc04c2411ddb1a1000ea68e967b,
title = "IFNgamma enhances microglial reactions to hippocampal axonal degeneration.",
abstract = "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.",
keywords = "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",
author = "Jensen, {M B} and Hegelund, {I V} and Lomholt, {N D} and B Finsen and T Owens",
year = "2000",
month = may,
day = "15",
language = "English",
volume = "20",
pages = "3612--21",
journal = "The Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "10",
}