title: Microglial P2X₇ receptor expression is accompanied by neuronal damage in the cerebral cortex of the APPswe/PS1dE9 mouse model of Alzheimer's disease.
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 Aβ increase and correlate with synaptotoxicity in AD.
authors.affiliation: Neuroscience Graduate Program, Ajou University School of Medicine, Suwon, Korea.
authors.forename: Hwan Goo
authors.initials: HG
authors.lastname: Lee
authors.forename: Sun Mi
authors.initials: SM
authors.lastname: Won
authors.forename: Byoung Joo
authors.initials: BJ
authors.lastname: Gwag
authors.forename: Yong Beom
authors.initials: YB
authors.lastname: Lee
mesh_terms: D000375:Aging; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides; D000818:Animals; D015153:Blotting, Western; D039481:CD11b Antigen / Q000276:immunology; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D015870:Gene Expression; D051379:Mice; D008822:Mice, Transgenic; D017628:Microglia / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D058225:Plaque, Amyloid; D017382:Reactive Oxygen Species / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000032:analysis; D058486:Receptors, Purinergic P2X7 / Q000235:genetics* / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D039481:CD11b Antigen; C105949:Pirb protein, mouse; D017382:Reactive Oxygen Species; D011971:Receptors, Immunologic; D058486:Receptors, Purinergic P2X7