Microglial $P2X_7$ receptor expression is accompanied by neuronal damage in the cerebral cortex of the $APP_{swe}$/PS1dE9 mouse model of Alzheimer's disease

• Published in: Experimental & molecular medicine 2011, Vol.43 (1), p.7-14
• Main Authors: Lee, Hwan-Goo, Won, Sun-Mi, Gwag, Byoung-Joo, Lee, Yong-Beom
• Format: Article
• Language: Korean
• ISSN: 1226-3613; 2092-6413

The possibility that $P2X_7$ receptor ($P2X_7R$) expression in microglia would mediate neuronal damage $via$ reactive oxygen species (ROS) production was examined in the $APP_{swe}$/PS1dE9 mouse model of Alzheimer's disease (AD). $P2X_7R$ was predominantly expressed in CD11b-immunopositive microglia from 3 months of age before A${\beta}$ plaque formation. In addition, $gp91^{phox}$, a catalytic subunit of NADPH oxidase, and ethidium fluorescence were detected in $P2X_7R$-positive microglial cells of animals at 6 months of age, indicating that $P2X_7$R-positive microglia could produce ROS. Postsynaptic density 95-positive dendrites showed significant damage in regions positive for $P2X_7R$ in the cerebral cortex of 6 month-old mice. Taken together, up-regulation of $P2X_7R$ activation and ROS production in microglia are parallel with A${\beta}$ increase and correlate with synaptotoxicity in AD.