Modulation of microglial metabolism facilitates regeneration

[frodo]

Modulation of microglial metabolism facilitates regeneration

https://www.sciencedirect.com/science/a ... 422300665X

Highlights

● Microglia loaded with lipid adopt a phagocytosis-enhanced microglia (PEMs) phenotype.
● Rosiglitazone helps microglia adopt myelination-associated microglia (MAMs) phenotype.
● Rosiglitazone facilitates glucose metabolism conversion by enhancing PPAR-γ signaling.


Summary

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 multiple sclerosis patients by integrating public sn-RNA-Seq data.

Microglia adopt a PEMs phenotype during the early phase of demyelinated lesions, predominated in proinflammatory responses and aggravated glycolysis, while MAMs mainly emerged during the later phase, with regenerative signatures and enhanced oxidative phosphorylation.

Additionally, microglial triggering receptor expressed on myeloid cells 2 (Trem2) was greatly involved in the phenotype transition in demyelination, but not indispensable for microglia transition towards 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.