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Activation of group II metabotropic glutamate receptors underlies microglial reactivity and neurotoxicity following stimulation with chromogranin A, a peptide up‐regulated in Alzheimer's disease
Author(s) -
Taylor D. L.,
Diemel L. T.,
Cuzner M. L.,
Pocock J. M.
Publication year - 2002
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 - 10.1046/j.1471-4159.2002.01062.x
Subject(s) - neurotoxicity , metabotropic glutamate receptor , microglia , metabotropic glutamate receptor 2 , glutamate receptor , chromogranin a , metabotropic receptor , receptor , neuroprotection , metabotropic glutamate receptor 1 , alzheimer's disease , biology , neuroscience , pharmacology , chemistry , medicine , endocrinology , inflammation , toxicity , disease , immunohistochemistry
Regulation of microglial reactivity and neurotoxicity is critical for neuroprotection in neurodegenerative diseases. Here we report that microglia possess functional group II metabotropic glutamate receptors, expressing mRNA and receptor protein for mGlu2 and mGlu3, negatively coupled to adenylate cyclase. Two different agonists of these receptors were able to induce a neurotoxic microglial phenotype which was attenuated by a specific antagonist. Chromogranin A, a secretory peptide expressed in amyloid plaques in Alzheimer's disease, activates microglia to a reactive neurotoxic phenotype. Chromogranin A‐induced microglial activation and subsequent neurotoxicity may also involve an underlying stimulation of group II metabotropic glutamate receptors since their inhibition reduced chromogranin A‐induced microglial reactivity and neurotoxicity. These results show that selective inhibition of microglial group II metabotropic glutamate receptors has a positive impact on neuronal survival, and may prove a therapeutic target in Alzheimer's disease.