The present address of David Baker is the Neuroscience Centre, Institute of Cell and Molecular Sciences, Queen Mary University of London, 4 Newark Street, London E1 2AT, UK.
Myelin-induced microglial neurotoxicity can be controlled by microglial metabotropic glutamate receptors
Article first published online: 14 APR 2008
© 2008 The Authors. Journal Compilation © 2008 International Society for Neurochemistry
Journal of Neurochemistry
Volume 106, Issue 1, pages 442–454, July 2008
How to Cite
Pinteaux-Jones, F., Sevastou, I. G., Fry, V. A. H., Heales, S., Baker, D. and Pocock, J. M. (2008), Myelin-induced microglial neurotoxicity can be controlled by microglial metabotropic glutamate receptors. Journal of Neurochemistry, 106: 442–454. doi: 10.1111/j.1471-4159.2008.05426.x
- Issue published online: 14 APR 2008
- Article first published online: 14 APR 2008
- Received September 25, 2007; revised manuscript received February 20, 2008; accepted March 28, 2008.
- glutamate receptor;
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.