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Updated: Jun 27, 2025
Three-dimensional Confocal Analysis of Microglia/macrophage Markers of Polarization in Experimental Brain Injury
Published on: September 4, 2013
TET1 mediated m5C modification of RelB aggravates cerebral ischemia/reperfusion-induced neuroinflammation through
Yan Lin1, Mei Liu2, Pinghuan Deng3
1Department of Neurology, Sichuan Provincial People's Hospital, School of Medicine, University of Elctronic Science and Technology of China, 32 2rd Setion of Yihuan Road West, Qingyang District, Chengdu, 610072, Sichuan Province, China.
Abstract:
Microglia mediated neuroinflammation is one of the major contributors to brain damage in cerebral ischemia reperfusion injury (CI/RI). Recently, RNA modification was found to contribute to the regulation of microglia polarization and the subsequent development of cerebral I/R neuroinflammation. Herein, we investigated the effect and mechanism of m5C RNA modification in the microglia induced CI/RI neuroinflammation. We found that the m5C RNA modification levels decreased in the primary microglia isolated from a mouse model of intraluminal middle cerebral artery occlusion/reperfusion (MCAO/R) and the BV2 microglial cells subjected to oxygen-glucose deprivation and reoxygenation (OGD/R), and this change was accompanied by an increase in the M1/M2 polarization ratio. Furthermore, the expression of m5C demethylase TET1 in microglia increased, which promoted M1 polarization but impeded M2 polarization. Mechanistically, the higher TET1 expression decreased the m5C modification level of RelB and enhanced its mRNA stability, which subsequently increased the M1/M2 polarization ratio. In conclusion, this study provides insight into the role of m5C RNA modification in the pathogenesis of cerebral I/R neuroinflammation and may deepen our understanding on clinical therapy targeting the TET1-RelB axis.
Insights
Reduced m5C RNA modification in microglia exacerbates brain damage after cerebral ischemia reperfusion injury. Increased TET1 demethylase promotes M1 polarization via the TET1-RelB axis, worsening neuroinflammation.
Area of Science:
- Neuroscience
- Molecular Biology
- Immunology
Background:
- Microglia-mediated neuroinflammation is a key factor in brain damage following cerebral ischemia reperfusion injury (CI/RI).
- RNA modifications are increasingly recognized for their role in regulating microglial polarization and neuroinflammation.
Purpose of the Study:
- To investigate the role and mechanism of m5C RNA modification in microglia-driven CI/RI neuroinflammation.
- To explore the impact of m5C RNA modification on microglial polarization in the context of CI/RI.
Main Methods:
- Utilized a mouse model of intraluminal middle cerebral artery occlusion/reperfusion (MCAO/R).
- Employed oxygen-glucose deprivation and reoxygenation (OGD/R) in BV2 microglial cells.
- Assessed m5C RNA modification levels, microglial polarization (M1/M2 ratio), and TET1 expression.
- Investigated the effect of TET1 on RelB mRNA stability and m5C modification.
Main Results:
- Decreased m5C RNA modification levels were observed in microglia from MCAO/R mice and OGD/R BV2 cells.
- This decrease correlated with an increased M1/M2 polarization ratio.
- Upregulated TET1 expression in microglia promoted M1 polarization and inhibited M2 polarization.
- TET1 enhanced RelB mRNA stability by reducing its m5C modification, further increasing the M1/M2 ratio.
Conclusions:
- m5C RNA modification plays a critical role in the pathogenesis of cerebral I/R neuroinflammation.
- The TET1-RelB axis is a key molecular mechanism by which m5C modification influences microglial polarization in CI/RI.
- Targeting the TET1-RelB axis may offer a novel therapeutic strategy for cerebral I/R injury.
