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Myelin‐induced microglial neurotoxicity can be controlled by microglial metabotropic glutamate receptors
Author(s) -
PinteauxJones Fleur,
Sevastou Ioanna G.,
Fry Victoria A. H.,
Heales Simon,
Baker David,
Pocock Jennifer M.
Publication year - 2008
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.1471-4159.2008.05426.x
Subject(s) - metabotropic glutamate receptor , neuroscience , metabotropic glutamate receptor 5 , metabotropic receptor , metabotropic glutamate receptor 6 , glutamate receptor , metabotropic glutamate receptor 2 , metabotropic glutamate receptor 7 , metabotropic glutamate receptor 8 , chemistry , myelin , microglia , metabotropic glutamate receptor 1 , receptor , medicine , biology , central nervous system , biochemistry , inflammation
Microglia are present in an activated state in multiple sclerosis lesions. Incubation of primary cultured rat microglia with rat‐brain derived myelin (0.1–1 μg/mL) for 24 h induced microglial activation; cells displayed enhanced ED1 staining, expression of inducible nitric oxide synthase, production and release of the cytokine tumour necrosis factor‐α and glutamate release. Exposure of microglia to myelin induced the expression of neuronal caspases and ultimately neuronal death in cultured cerebellar granule cell neurons; neurotoxicity was directly because of microglial‐derived soluble toxins. Co‐incubation of microglia with agonists or antagonists of different metabotropic glutamate receptor (mGluR) subtypes ameliorated microglial neurotoxicity by inhibiting soluble neurotoxin production. Activation of microglial mGluR2 exacerbated myelin‐evoked neurotoxicity whilst activation of mGluR3 was protective as was activation of group III mGluRs. These data show that myelin‐induced microglial neurotoxicity can be prevented by regulation of mGluRs and suggest these receptors on microglia may be promising targets for therapeutic intervention in multiple sclerosis.