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Three-dimensional Confocal Analysis of Microglia/macrophage Markers of Polarization in Experimental Brain Injury
Published on: September 4, 2013
FAM19A3, a novel secreted protein, modulates the microglia/macrophage polarization dynamics and ameliorates cerebral
Yankun Shao1, Ting Deng2, Tong Zhang3
1Neurology Department, China-Japan Union Hospital, Jilin University, Changchun 130031, China.
Abstract:
In this study, we have identified FAM19A3 as a gene that is significantly upregulated in the microglia in the middle cerebral artery occlusion (MCAO) mouse model. FAM19A3 expression and secretion were promoted by M2 stimuli, and this indicated that FAM19A3 might be an M2-type gene. Indeed, recombinant FAM19A3 promoted M2 polarization and inhibited M1 polarization of microglia in vitro. Similarly, recombinant FAM19A3 promoted M2 polarization of microglia and macrophages in vivo, and attenuated cerebral ischemia in the MCAO mouse model. Thus, the newly-identified secreted protein FAM19A3 modulates the microglia/macrophage polarization dynamics and ameliorates cerebral ischemia.
Insights
Researchers found that FAM19A3, a novel secreted protein, promotes M2 polarization in microglia and macrophages. This finding suggests FAM19A3 may be a therapeutic target for mitigating cerebral ischemia.
Area of Science:
- Neuroscience
- Immunology
- Molecular Biology
Background:
- Microglia play a crucial role in the brain's immune response, with distinct M1 (pro-inflammatory) and M2 (anti-inflammatory/repair) phenotypes.
- Microglial polarization is critical in the pathogenesis and resolution of cerebral ischemia.
- The specific molecular regulators of microglial polarization in stroke remain incompletely understood.
Purpose of the Study:
- To identify novel genes and secreted proteins involved in microglial activation during cerebral ischemia.
- To investigate the role of the identified gene, FAM19A3, in regulating microglial polarization.
- To evaluate the therapeutic potential of FAM19A3 in a mouse model of cerebral ischemia.
Main Methods:
- Utilized the middle cerebral artery occlusion (MCAO) mouse model to induce cerebral ischemia.
- Analyzed gene expression in microglia, identifying FAM19A3 as significantly upregulated.
- Administered recombinant FAM19A3 in vitro and in vivo to assess its effects on microglial and macrophage polarization.
- Evaluated the impact of FAM19A3 on neurological deficits and infarct volume in the MCAO model.
Main Results:
- FAM19A3 was significantly upregulated in microglia from MCAO mice.
- M2 stimuli promoted FAM19A3 expression and secretion, suggesting it is an M2-type gene.
- Recombinant FAM19A3 promoted M2 polarization and inhibited M1 polarization of microglia and macrophages in vitro and in vivo.
- FAM19A3 administration attenuated cerebral ischemia in the MCAO mouse model.
Conclusions:
- FAM19A3 is a novel secreted protein that modulates microglia/macrophage polarization dynamics.
- FAM19A3 promotes an M2-like phenotype, shifting the balance away from pro-inflammatory M1 responses.
- FAM19A3 demonstrates therapeutic potential for ameliorating cerebral ischemia by influencing neuroinflammation.

