Frontiers in Neuroscience· 2026Q2
A purinergic receptor dominance model for microglial state transitions: balancing perturbation and restraint during neuroinflammation
- 0citations
- Q2SCImago
- 2026year
Short summary
A new model proposes that microglial state transitions during neuroinflammation are governed by the shifting balance between ATP- and adenosine-sensitive purinergic receptors, acting as a gauge for tissue stress intensity and duration.
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Key points
- Microglial state transitions in neuroinflammation are driven by the balance of purinergic receptors responding to ATP and adenosine.
- P2Y12 signaling supports surveillance, P2X4 mediates early injury responses, and A1/A2A receptors provide adenosine-linked regulation.
- Persistent or severe stress can activate P2X7 for inflammatory amplification, while high adenosine may engage A2B signaling.
- The model suggests microglia gauge tissue stress intensity, duration, and metabolic context via these upstream receptor systems.
AI-generated from the title and abstract; the full text is not read.
Abstract
Microglia show substantial functional heterogeneity during neuroinflammatory responses, yet the upstream mechanisms through which they interpret extracellular perturbation-associated signals and transition between functional states remain incompletely understood. Purinergic signaling is well positioned to serve as such an environmental sensing system because ATP is released rapidly from stressed or damaged cells and is subsequently metabolized to adenosine, generating an extracellular purine landscape that changes with the magnitude and persistence of tissue stress. We propose a Purinergic Receptor Dominance Model for microglial state transitions during neuroinflammation. Microglial responses are shaped by the changing balance among ATP- and adenosine-sensitive receptor systems. P2Y12-associated signaling supports physiological surveillance; P2X4 contributes to early injury responses; and A1 and A2A receptors provide temporally layered adenosine-linked regulation. Persistent or severe stress may recruit P2X7-associated inflammatory amplification. Under the high-adenosine conditions that can accompany prolonged stress or hypoxia, A2B-linked signaling may also become relevant. The model focuses on the upstream receptor systems through which microglia may gauge the intensity, duration, and metabolic context of tissue stress. It is presented as a testable organizing hypothesis that can be evaluated, refined, or rejected experimentally.
The authors' abstract, as published at the source. Frontiers in Neuroscience, 2026 · DOI ↗
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