Microglial P2X₇ receptor expression is accompanied by neuronal damage in the cerebral cortex of the APPswe/PS1dE9 mouse model of Alzheimer's disease

Exp Mol Med. 2011 Jan 31;43(1):7-14. doi: 10.3858/emm.2011.43.1.001.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging
  • Alzheimer Disease* / genetics
  • Alzheimer Disease* / metabolism
  • Alzheimer Disease* / pathology
  • Amyloid beta-Peptides
  • Animals
  • Blotting, Western
  • CD11b Antigen / immunology
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / pathology*
  • Disease Models, Animal
  • Gene Expression
  • Mice
  • Mice, Transgenic
  • Microglia / metabolism*
  • Microglia / pathology
  • Neurons / metabolism
  • Neurons / pathology*
  • Plaque, Amyloid
  • Reactive Oxygen Species / metabolism*
  • Receptors, Immunologic / analysis
  • Receptors, Purinergic P2X7 / genetics*
  • Receptors, Purinergic P2X7 / metabolism

Substances

  • Amyloid beta-Peptides
  • CD11b Antigen
  • Pirb protein, mouse
  • Reactive Oxygen Species
  • Receptors, Immunologic
  • Receptors, Purinergic P2X7