期刊
NEUROSCIENCE LETTERS
卷 505, 期 2, 页码 140-145出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.neulet.2011.10.007
关键词
Fibrinogen; mGluR5; Microglia; Neurotoxicity
资金
- MRC
Microglial activation and blood brain barrier dysfunction are significant hallmarks in an array of neurodegenerative disorders. A leaky blood brain barrier potentially allows infiltration of blood-borne proteins into the CNS parenchyma, and previous studies have shown that the blood borne protein fibrinogen (FG) can activate microglia to produce a neurotoxic phenotype. Here we show that FG-mediated neurotoxicity and ERK1/2 phosphorylation in neuronal cultures is significantly attenuated by activation of metabotropic glutamate receptor 5 (mGluR5) but not mGluR2. Furthermore, FG-mediated microglial activation was down-regulated by direct mGluR5 activation on these cells but not by mGluR2, suggesting that targeting microglial mGluR5 provides neuronal protection against blood protein-triggered innate inflammatory responses. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
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