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Published on: September 4, 2013
P2Y6R Inhibition Induces Microglial M2 Polarization by Promoting PINK1/Parkin-Dependent Mitophagy After Spinal Cord
Jiezhao Lin1,2, Yuanfang Sun1, Haoran Huang1
1Department of Spinal Surgery, Orthopedic Medical Center, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China.
Abstract:
Secondary injury presents a significant hurdle to neural regeneration following spinal cord injury (SCI), primarily driven by inflammation in which microglial cells play a crucial role. Despite the growing interest in mitophagy, studies on its occurrence post-spinal cord injury, particularly within microglial cells, are scarce. While P2Y6R has been implicated in inflammation regulation in various neurological conditions, its specific role in SCI remains uncertain. Our study revealed an upregulation of P2Y6R expression following SCI notably in microglial cells. Treatment with the P2Y6R-specific inhibitor, MRS2578, in mice facilitated M2 polarization of microglial cells and alleviated secondary damage, ultimately enhancing neural regeneration and functional recovery. In an in vitro BV2 inflammation model, our findings indicate that P2Y6R inhibition induced M2 polarization of BV2 cells and reduced neuroinflammation through PINK/Parkin-dependent mitophagy activation. In summary, our results underscore the potential of P2Y6R inhibition in promoting mitophagy-induced M2 polarization of microglial cells, thereby ameliorating secondary injury following spinal cord injury.
Insights
Inhibiting P2Y6R in spinal cord injury (SCI) promotes microglial M2 polarization and mitophagy, reducing secondary damage and enhancing neural regeneration. This offers a potential therapeutic strategy for SCI recovery.
Area of Science:
- Neuroscience
- Immunology
- Regenerative Medicine
Background:
- Secondary injury, driven by neuroinflammation involving microglial cells, impedes neural regeneration after spinal cord injury (SCI).
- The role of mitophagy in microglial cells post-SCI and the specific function of P2Y6R in this context are not well understood.
Purpose of the Study:
- To investigate the role of P2Y6R in microglial cells following SCI.
- To explore the therapeutic potential of P2Y6R inhibition in promoting neural regeneration and functional recovery post-SCI.
Main Methods:
- Upregulation of P2Y6R expression in microglial cells post-SCI was assessed.
- Mice with SCI were treated with a P2Y6R inhibitor (MRS2578).
- An in vitro BV2 microglial inflammation model was used to study P2Y6R inhibition effects on mitophagy and neuroinflammation.
Main Results:
- P2Y6R expression was upregulated in microglial cells after SCI.
- MRS2578 treatment promoted M2 polarization of microglial cells, reduced secondary damage, and improved functional recovery in mice.
- In vitro, P2Y6R inhibition induced M2 polarization and reduced neuroinflammation via PINK/Parkin-dependent mitophagy activation.
Conclusions:
- P2Y6R inhibition promotes M2 polarization of microglial cells through mitophagy.
- Targeting P2Y6R represents a promising therapeutic approach to mitigate secondary injury and enhance neural regeneration after SCI.
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