CD300f is required for efficient lipid handling during cuprizone-induced demyelination

CD300f-deficient mice show exacerbated cuprizone-induced demyelination with increased microglial lipid droplet accumulation, impaired microglial responses, reduced remyelination, and motor coordination deficits.

• Why it matters: Microglia must sense and process myelin-derived lipids during demyelination, but how lipid handling is coordinated remains unclear, limiting therapeutic targeting.
• What they did: In the cuprizone model, the study compared CD300f-deficient versus control mice and performed bulk RNA sequencing of corpus callosum at peak demyelination to assess microglial states and lipid/metabolic pathways.
• The result: Transcriptional shifts linked to homeostatic, DAM, and foamy microglial signatures and lysosomal/phagocytosis/inflammation/lipid metabolism were associated with marked microglial lipid droplet accumulation and enrichment of chronic lesion–linked microglial states.

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