Upregulated Expression of Purinergic P2X 7 Receptor in Alzheimer Disease and Amyloid-β Peptide-Treated Microglia and in Peptide-Injected Rat Hippocampus
Abstract
The expression of the purinergic receptor subtype P2X(7)R, a nonselective cationic channel activated by high levels of adenosine triphosphate (ATP), has been studied in adult microglia obtained from Alzheimer disease (AD) and nondemented (ND) brains, in fetal human microglia exposed to Abeta(1-42) peptide and in vivo in Abeta(1-42)-injected rat hippocampus. Semiquantitative reverse transcriptase-polymerase chain reaction showed enhanced expression (increase of 70%) of P2X(7)R in AD microglia compared with ND cells (analysis of 6 AD and 8 ND cases). Immunohistochemical analysis showed prominent P2X(7)R expression in association with Abeta plaques and localized to HLA-DR-immunoreactive microglia. In cultured fetal human microglia, cells exposed to Abeta(1-42) (5 microM for 18 hours) had significantly elevated levels of P2X(7)R (by 106%) compared with untreated cells. Amplitudes of Ca(2+) responses in these cells, induced by the selective P2X(7)R agonist BzATP, were increased by 145% with Abeta(1-42) pretreatment relative to control (no peptide pretreatment) and were largely blocked if the P2X(7)R inhibitor-oxidized ATP (oxATP) was added with peptide in pretreatment solution. In vivo, double immunostaining analysis showed considerable P2X(7)R colocalized with microglia after injection of Abeta(1-42) (1 nmol) into rat hippocampus. The overall results suggest roles of P2X(7)R in mediating microglial purinergic inflammatory responses in AD brain.
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P2RX7 levels are elevated in AD brains.
“Intriguingly, P2RX7 levels are elevated in AD brains (McLarnon et al. 2006).”
From miR‐186 is decreased in aged brain and suppresses <scp>BACE</scp>1 expression (2016) · cites this paper as McLarnon et al. 2006
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- Authors
- McLarnon, J. G., Ryu, J. K., Walker, D. G., & Choi, H. B.
- Affiliations
- University of British Columbia (CA)
- Banner Sun Health Research Institute (US)
- Corresponding author
- McLarnon, James G.
- Venue
- Journal of Neuropathology & Experimental Neurology
- Publisher
- Oxford University Press (OUP)
- Published
- 2006-11
- Volume
- 65
- Issue
- 11
- Pages
- 1090-1097
- ISSN
- 0022-3069 (ISSN-L)
- 1554-6578
- OpenAlex
- W2069219003
- Cited by
- 281
- References
- 1
- Citations by year
- 2026: 14 · 2025: 19 · 2024: 21 · 2023: 18 · 2022: 21 · 2021: 29 · 2020: 15 · 2019: 13 · 2018: 12 · 2017: 9 · 2016: 8 · 2015: 14 · 2014: 9 · 2013: 13 · 2012: 15
- FWCI
- 4.25
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neuropathology & Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG18345, R01AG018345)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- P2X7 receptor, Alzheimer's disease, amyloid-beta, microglia, purinergic signaling, ATP, BzATP, oxidized ATP, calcium response, HLA-DR, amyloid plaques, hippocampus, neuroinflammation
- MeSH terms
- Adenosine Triphosphate, Affinity Labels, Alzheimer Disease, Animals, Calcium, Hippocampus, HLA-DR Antigens, Humans, Immunohistochemistry, Microscopy, Fluorescence, Peptides, Up-Regulation, Amyloid beta-Peptides, Microglia, Receptors, Purinergic P2, Reverse Transcriptase Polymerase Chain Reaction, Rats, Receptors, Purinergic P2X7
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