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The possibility that P2X₇ receptor (P2X₇R) expression in microglia would mediate neuronal damage via reactive oxygen species (ROS) production was examined in the APPswe/PS1dE9 mouse model of Alzheimer's disease (AD). P2X7R was predominantly expressed in CD11b-immunopositive microglia from 3 months of age before Abeta plaque formation. In addition, gp91phox, a catalytic subunit of NADPH oxidase, and ethidium fluorescence were detected in P2X₇R-positive microglial cells of animals at 6 months of age, indicating that P2X₇R-positive microglia could produce ROS. Postsynaptic density 95-positive dendrites showed significant damage in regions positive for P2X₇R in the cerebral cortex of 6 month-old mice. Taken together, up-regulation of P2X₇R activation and ROS production in microglia are parallel with Aβ increase and correlate with synaptotoxicity in AD.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3041940PMC
http://dx.doi.org/10.3858/emm.2011.43.1.001DOI Listing

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