Fig. 4: Decreased N-AS in APP/PS1 microglia is restored with N-AS treatment, converting neurodegenerative microglia to phagocytic microglia via N-AS-triggered SPMs.

a Scheme of experimental procedure. Daily administration of N-AS or vehicle subcutaneously to 7-months-old APP/PS1 mice for 8 weeks. b Representative chromatograms of N-AS and quantification in microglia and neuron derived from WT, APP/PS1 and APP/PS1 mice treated by N-AS (n = 6 per group). c Representative photomicrograph and quantification and quantification of microglia (Iba1, red) with ac-S565 (green) and COX2 (blue) in cortex of WT, APP/PS1, and APP/PS1 treated with N-AS mice. Scale bars, 20 μm (n = 6 per group). d Western blot analysis for ac-S565 and total COX2 in microglia and neuron derived from WT, APP/PS1, and APP/PS1 injected with N-AS mice (n = 6 per group). e Top, gating strategy for detection of CD86⁺CD206⁻(pro-inflammatory microglia), CD86⁺CD206⁺, and CD86⁻CD206⁺ (anti-inflammatory microglia) cells within brain cell populations. Bottom, graph displaying the calculated percentage of CD86⁺CD206⁻(pro-inflammatory microglia), CD86⁺CD206⁺, and CD86⁻CD206⁺ (anti-inflammatory microglia) cells in WT, APP/PS1, and APP/PS1 treated with N-AS mice (n = 6–7 mice per group). f Heatmap analysis of RNA seq expression data of microglia isolated WT, APP/PS1, and APP/PS1 injected with N-AS mice (n = 3–4 per group; each sample is a pool of two mice.). g–i GO term enrichment analysis of biological process (GOTERM_BP) (g), molecular function (GOTERM_MF) (h), and KEGG pathway enrichment analysis (i) was performed using DAVID Bioinformatics Resources 6.8. All data analysis was done at 9-months-old mice. b–e One-way analysis of variance. All error bars indicate s.e.m. Source data are provided as a Source data file.