Microglial P2X7 receptor expression is accompanied by neuronal damage in the cerebral cortex of the APPswe/PS1dE9 mouse model of Alzheimer's disease.
10.3858/emm.2011.43.1.001
- Author:
Hwan Goo LEE
1
;
Sun Mi WON
;
Byoung Joo GWAG
;
Yong Beom LEE
Author Information
1. Neuroscience Graduate Program, Ajou University School of Medicine, Suwon 443-721, Korea. yblee@ajou.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
adenosine triphosphate;
Alzheimer disease;
amyloid beta-protein precursor;
Dlgh4 protein, mouse;
microglia;
reactive oxygen species;
receptors, purinergic P2X7
- MeSH:
Aging;
*Alzheimer Disease/genetics/metabolism/pathology;
Amyloid beta-Peptides;
Animals;
Antigens, CD11b/immunology;
Blotting, Western;
Cerebral Cortex/metabolism/*pathology;
Disease Models, Animal;
Gene Expression;
Mice;
Mice, Transgenic;
Microglia/*metabolism/pathology;
Neurons/metabolism/*pathology;
Plaque, Amyloid;
Reactive Oxygen Species/*metabolism;
Receptors, Immunologic/analysis;
Receptors, Purinergic P2X7/*genetics/metabolism
- From:Experimental & Molecular Medicine
2011;43(1):7-14
- CountryRepublic of Korea
- Language:English
-
Abstract:
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 Abeta increase and correlate with synaptotoxicity in AD.
