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P2X~7~ receptors on microglial cells mediate injury to cortical neurons in vitro by Stephen D. Skaper; Laura Facci; Ainsley A. Culbert; Nicholas A. Evans; Iain Chessell; John B. Davis; Jill C. Richardson is a Neuroscience article available to read on EtoBox.
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## Abstract The P2X~7~ receptor has been implicated in the release of cytokines and in the induction of cell death, and is up‐regulated in a transgenic mouse model of Alzheimer's disease. Using cocultures of rat cortical neurons and microglia, we show that ATP and the more potent P2X~7~ agonist benzoylbenzoyl‐ATP (BzATP) cause neuronal cell injury. The deleterious effects of BzATP‐treated microglia were prevented by nonselective P2X antagonists (PPADS and oxidized ATP) and by the more selective P2X~7~ antagonist Brilliant Blue G. Similar concentrations of BzATP caused release of superoxide and nitric oxide from isolated microglia, and neuronal cell injury was attenuated by a superoxide dismutase mimetic and by a peroxynitrite decomposition catalyst, suggesting a role for reactive oxide species. Cocultures composed of wild‐type cortical neurons, and microglia from P2X~7~ receptor‐deficient mice failed to exhibit neuronal cell injury in the presence of BzATP, but retained sensitivity to injury when microglia were derived from genotypically matched normal (P2X~7~^+/+^ mice), thereby establishing P2X~7~ involvement in the injury process. P2X~7~ receptor activation on microglia thus app
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- Author
- Stephen D. Skaper; Laura Facci; Ainsley A. Culbert; Nicholas A. Evans; Iain Chessell; John B. Davis; Jill C. Richardson
- Publisher
- John Wiley and Sons; Wiley (John Wiley & Sons); John Wiley & Sons Inc.; Wiley; Research Square (ISSN 0894-1491)
- Published
- 2006
- Language
- EN
- Field
- Neuroscience (Life Sciences)