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IL‐4 attenuates the neuroinflammation induced by amyloid‐β in vivo and in vitro
Author(s) -
Lyons Anthony,
Griffin Rebecca J,
Costelloe Ceire E,
Clarke Rachael M,
Lynch Marina A
Publication year - 2007
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2006.04370.x
Subject(s) - long term potentiation , neuroinflammation , minocycline , hippocampal formation , microglia , perforant path , chemistry , intracellular , hippocampus , microbiology and biotechnology , neuroscience , biology , immunology , biochemistry , inflammation , receptor , antibiotics
Abstract It has been shown that Aβ inhibits long‐term potentiation (LTP) in the rat hippocampus and this is accompanied by an increase in hippocampal concentration of IL‐1β. Aβ also increases microglial activation, which is the likely cell source of IL‐1β. Because IL‐4 attenuates the effects of IL‐1β in hippocampus, and microglial activation is inhibited by minocycline, we assessed the ability of both IL‐4 and minocycline to modulate the effects of Aβ on LTP and IL‐1β concentration. Following treatment with Aβ, IL‐4 or minocycline, rats were assessed for their ability to sustain LTP in perforant path‐granule cell synapses. We report that the Aβ‐induced inhibition of LTP was associated with increases in expression of MHCII, JNK phosphorylation and IL‐1β concentration, and that these changes were attenuated by treatment of rats with IL‐4 and minocycline. We also report that Aβ‐induced increases in expression of MHCII and IL‐1β 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‐1β concentration mediate the inhibitory effect of Aβ on LTP and indicate that IL‐4, by down‐regulating glial cell activation, antagonizes the effects of Aβ.