Jul 22, 2005

Modulator effects of interleukin-1beta and tumor necrosis factor-alpha on AMPA-induced excitotoxicity in mouse organotypic hippocampal slice cultures

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Liliana BernardinoJ Zimmer

Abstract

The inflammatory cytokines interleukin-1beta and tumor necrosis factor-alpha (TNF-alpha) have been identified as mediators of several forms of neurodegeneration in the brain. However, they can produce either deleterious or beneficial effects on neuronal function. We investigated the effects of these cytokines on neuronal death caused by exposure of mouse organotypic hippocampal slice cultures to toxic concentrations of AMPA. Either potentiation of excitotoxicity or neuroprotection was observed, depending on the concentration of the cytokines and the timing of exposure. A relatively high concentration of mouse recombinant TNF-alpha (10 ng/ml) enhanced excitotoxicity when the cultures were simultaneously exposed to AMPA and to this cytokine. Decreasing the concentration of TNF-alpha to 1 ng/ml resulted in neuroprotection against AMPA-induced neuronal death independently on the application protocol. By using TNF-alpha receptor (TNFR) knock-out mice, we demonstrated that the potentiation of AMPA-induced toxicity by TNF-alpha involves TNF receptor-1, whereas the neuroprotective effect is mediated by TNF receptor-2. AMPA exposure was associated with activation and proliferation of microglia as assessed by macrophage antigen-1 and bro...Continue Reading

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Mentioned in this Paper

AMPA, (S)-Isomer, Monohydrobromide
Alpha-Neurotoxins
Immunohistochemistry
Tumor Necrosis Factor-alpha
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
Organ Culture Techniques
Tumor Necrosis Factor Receptor
Interleukin-1
Neurons
Brain

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