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Updated: Jun 25, 2026
Assessing Retinal Microglial Phagocytic Function In Vivo Using a Flow Cytometry-based Assay
Published on: October 18, 2016
UDP facilitates microglial phagocytosis through P2Y6 receptors
1Department of Molecular and System Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi Higashi, Fukuoka 812-8582 Japan. kazuinouejp@ybb.ne.jp
Abstract:
Microglia engage in the clearance of dead cells or dangerous debris. When neighboring cells are injured, the cells release or leak ATP into extracellular space and microglia rapidly move toward or extend a process to the nucleotides as chemotaxis through P2Y12 receptors. In the meanwhile, microglia express the metabotropic P2Y6 receptors, the activation of which by uridine 5'-diphosphate (UDP) triggers microglial phagocytosis in a concentration-dependent fashion. UDP/UTP was leaked when hippocampal neurons were damaged by kainic acid in vivo and in vitro. Systemic administration of kainic acid in rats resulted in neuronal cell death in the hippocampal CA1 and CA3 regions, where increases in mRNA for P2Y6 receptors in activated microglia. Thus, the P2Y6 receptor is upregulated when neurons are damaged, and would function as a sensor for phagocytosis by sensing diffusible UDP signals.
Insights
Microglia use P2Y6 receptors to sense damaged neuron signals like uridine 5'-diphosphate (UDP), triggering phagocytosis to clear cellular debris. This process is crucial for brain repair after neuronal injury.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglia are key immune cells in the central nervous system, responsible for clearing cellular debris and dead cells.
- Microglial migration and phagocytosis are critical processes in response to neuronal injury.
- Extracellular nucleotides, such as ATP and UDP, act as signaling molecules in the brain.
Purpose of the Study:
- To investigate the role of P2Y6 receptors in microglial phagocytosis following neuronal damage.
- To determine if P2Y6 receptor expression is altered in microglia during neuroinflammation.
Main Methods:
- In vivo and in vitro models of neuronal damage using kainic acid.
- Assessment of microglial activation and migration towards nucleotide signals.
- Quantitative analysis of P2Y6 receptor mRNA expression in microglia.
Main Results:
- Kainic acid-induced neuronal damage led to the leakage of UDP/UTP in hippocampal regions.
- P2Y6 receptor mRNA levels were significantly increased in activated microglia in damaged hippocampal areas.
- Microglial activation of P2Y6 receptors by UDP triggered concentration-dependent phagocytosis.
Conclusions:
- The P2Y6 receptor is upregulated in microglia upon neuronal damage.
- P2Y6 receptors function as critical sensors for diffusible UDP signals, mediating microglial phagocytosis.
- Targeting P2Y6 receptors may offer therapeutic strategies for conditions involving neuronal injury and inflammation.
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