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Updated: Jul 31, 2025
Assessing Microglial Phagocytosis of Myelin Debris in vitro Under Repeated Magnetic Stimulation
Published on: June 17, 2025
Modulation of microglial metabolism facilitates regeneration in demyelination
Chuan Qin1, Sheng Yang1, Man Chen1
1Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Abstract:
Microglia exhibit diverse phenotypes in various central nervous system disorders and metabolic pathways exert crucial effects on microglial activation and effector functions. Here, we discovered two novel distinct microglial clusters, functionally associated with enhanced phagocytosis (PEMs) and myelination (MAMs) respectively, in human patients with multiple sclerosis by integrating public snRNA-seq data. Microglia adopt a PEMs phenotype during the early phase of demyelinated lesions, predominated in pro-inflammatory responses and aggravated glycolysis, while MAMs mainly emerged during the later phase, with regenerative signatures and enhanced oxidative phosphorylation. In addition, microglial triggering receptor expressed on myeloid cells 2 (Trem2) was greatly involved in the phenotype transition in demyelination, but not indispensable for microglia transition toward PEMs. Rosiglitazone could promote microglial phenotype conversion from PEMs to MAMs, thus favoring myelin repair. Taken together, these findings provide insights into therapeutic interventions targeting immunometabolism to switch microglial phenotypes and facilitate regenerative capacity in demyelination.
Insights
Researchers identified two microglial phenotypes in multiple sclerosis: pro-inflammatory phagocytic microglia (PEMs) and regenerative myelinating microglia (MAMs). A drug promoted the switch from PEMs to MAMs, aiding myelin repair.
Area of Science:
- Neuroimmunology
- Cellular Metabolism
- Neurodegenerative Diseases
Background:
- Microglia, the immune cells of the central nervous system, display diverse phenotypes.
- Metabolic pathways significantly influence microglial activation and function in neurological disorders.
- Understanding microglial heterogeneity is crucial for developing effective therapies for central nervous system diseases.
Purpose of the Study:
- To identify and characterize distinct microglial clusters in human multiple sclerosis.
- To investigate the functional roles and metabolic profiles of these microglial phenotypes.
- To explore therapeutic strategies for modulating microglial phenotypes to promote myelin repair.
Main Methods:
- Integration of public single-nucleus RNA sequencing (snRNA-seq) data from human multiple sclerosis patients.
- Bioinformatic analysis to identify distinct microglial clusters.
- Assessment of metabolic pathways (glycolysis, oxidative phosphorylation) and gene expression related to microglial function.
Main Results:
- Discovery of two novel microglial clusters: phagocytic (PEMs) and myelinating (MAMs).
- PEMs are associated with early demyelination, inflammation, and glycolysis; MAMs with later stages, regeneration, and oxidative phosphorylation.
- Microglial triggering receptor expressed on myeloid cells 2 (Trem2) influences phenotype transition, but is not essential for PEM development.
- Rosiglitazone treatment facilitated the conversion of PEMs to MAMs, promoting myelin repair.
Conclusions:
- Microglial phenotypes dynamically change during demyelination, reflecting distinct metabolic states.
- Targeting immunometabolism offers a promising strategy to enhance microglial regenerative functions in demyelinating diseases.
- Pharmacological modulation of microglial phenotype holds potential for therapeutic intervention in multiple sclerosis.
