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Updated: May 9, 2025
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Two-photon Imaging of Cellular Dynamics in the Mouse Spinal Cord
Published on: February 22, 2015
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TREM2 Impedes Recovery After Spinal Cord Injury by Regulating Microglial Lysosomal Membrane Permeabilization-Mediated
Tianlun Zhao1,2, Jiawei Di1,2, Yu Kang1,2
1Department of Spine Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
Cell Proliferation
|May 5, 2025
Summary
TREM2 deficiency enhances microglial autophagy and lysosomal function after spinal cord injury. This promotes functional recovery and offers a potential gene therapy strategy for central nervous system disorders.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglia are key immune responders in the central nervous system (CNS).
- TREM2 is highly expressed in microglia and influences their function.
- The role of TREM2 in spinal cord injury (SCI) remains unexplored.
Purpose of the Study:
- Investigate the mechanism of TREM2 in SCI.
- Determine TREM2's role in microglial regulation of neuroinflammation.
- Explore therapeutic potential for CNS disorders.
Main Methods:
- Single-cell sequencing in wild-type and Trem2 knockout mice pre- and post-SCI.
- Analysis of lysosomal and autophagy pathways.
- In vitro and in vivo experiments assessing Trem2 silencing effects on autophagy and SCI recovery.
- Functional and histological assessments including gait analysis and tissue staining.
Main Results:
- TREM2 deficiency activates lysosome, autophagy, and membrane-related pathways in microglia post-SCI.
- TREM2 knockout reduces TFEB nuclear translocation by decreasing Syk phosphorylation.
- Silencing Trem2 promotes autophagy by repairing lysosomal membrane permeabilization.
- Increased autophagy rescues microglia and improves functional and histological recovery after SCI.
Conclusions:
- Microglial lysosomal autophagy is regulated in a TREM2-dependent lysosomal membrane permeabilization (LMP) manner.
- Targeting microglial autophagy presents a promising therapeutic strategy for SCI.
- This study provides a basis for gene therapy approaches in lysosome-related CNS disorders.
