• Anthony Lyons, Rebecca J Griffin, Ceire E Costelloe, Rachael M Clarke, and Marina A Lynch.
• Trinity College Institute for Neuroscience, Physiology Department, Trinity College, Dublin, Ireland.
• J. Neurochem. 2007 May 1;101(3):771-81.

AbstractIt has been shown that Abeta inhibits long-term potentiation (LTP) in the rat hippocampus and this is accompanied by an increase in hippocampal concentration of IL-1beta. Abeta also increases microglial activation, which is the likely cell source of IL-1beta. Because IL-4 attenuates the effects of IL-1beta in hippocampus, and microglial activation is inhibited by minocycline, we assessed the ability of both IL-4 and minocycline to modulate the effects of Abeta on LTP and IL-1beta concentration. Following treatment with Abeta, IL-4 or minocycline, rats were assessed for their ability to sustain LTP in perforant path-granule cell synapses. We report that the Abeta-induced inhibition of LTP was associated with increases in expression of MHCII, JNK phosphorylation and IL-1beta concentration, and that these changes were attenuated by treatment of rats with IL-4 and minocycline. We also report that Abeta-induced increases in expression of MHCII and IL-1beta were similarly attenuated by IL-4 and minocycline in glial cultures prepared from neonatal rats. These data suggest that glial cell activation and the consequent increase in IL-1beta concentration mediate the inhibitory effect of Abeta on LTP and indicate that IL-4, by down-regulating glial cell activation, antagonizes the effects of Abeta.

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