Related Experiment Video
Updated: Jun 24, 2026
Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
Activation of microglia by amyloid {beta} requires P2X7 receptor expression
Juana M Sanz1, Paola Chiozzi, Davide Ferrari
1Department of Clinical and Experimental Medicine, University of Ferrara, Italy.
Abstract:
Extracellular ATP is a mediator of intercellular communication and a danger signal. Release of this and other nucleotides modulates microglia responses via P2Y and P2X receptors, among which the P2X(7) subtype stands out for its proinflammatory activity and for up-regulation in a transgenic model of Alzheimer disease and in brains from Alzheimer disease patients. Here we show that amyloid beta (Abeta) triggered increases in intracellular Ca(2+) ([Ca(2+)](i)), ATP release, IL-1beta secretion, and plasma membrane permeabilization in microglia from wild-type but not from P2X(7)-deleted mice. Likewise, intra-hippocampal injection of Abeta caused a large accumulation of IL-1beta in wild-type but not in P2X(7)(-/-) mice. These observations suggest that Abeta activates a purinergic autocrine/paracrine stimulatory loop of which the P2X(7) receptor is an obligate component. Identification of the P2X(7) receptor as a non-dispensable factor of Abeta-mediated microglia stimulation may open new avenues for the treatment of Alzheimer disease.
Insights
Extracellular ATP and amyloid beta trigger inflammatory responses in microglia via the P2X7 receptor. Blocking this receptor may offer new Alzheimer disease treatments.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Extracellular ATP signals danger and modulates microglia via P2Y and P2X receptors.
- The P2X7 receptor subtype is proinflammatory and upregulated in Alzheimer disease models and patients.
Purpose of the Study:
- To investigate the role of the P2X7 receptor in amyloid beta-mediated microglial activation.
- To elucidate the purinergic signaling pathway involved in Alzheimer disease pathogenesis.
Main Methods:
- Utilized microglia from wild-type and P2X7-deleted mice.
- Administered amyloid beta to cell cultures and performed intra-hippocampal injections in mice.
- Measured intracellular calcium, ATP release, IL-1beta secretion, and plasma membrane permeability.
Main Results:
- Amyloid beta induced calcium increase, ATP release, IL-1beta secretion, and membrane permeabilization in wild-type microglia, but not in P2X7-deleted microglia.
- Intra-hippocampal amyloid beta injection led to significant IL-1beta accumulation in wild-type mice, but not in P2X7 knockout mice.
Conclusions:
- Amyloid beta activates a P2X7 receptor-dependent purinergic signaling loop in microglia.
- The P2X7 receptor is essential for amyloid beta-induced microglial stimulation, suggesting it as a therapeutic target for Alzheimer disease.
