Fig. 6: Cox2–Ptges inhibition rescues enhanced neurodegeneration and accelerated prion disease after NG2 glia depletion.

a,b, NeuN immunofluorescence (a) and quantification (b) showing that enhanced neurodegeneration in prion-infected, NG2-glia-depleted (CP673451) Tga20 COCS can be rescued by treatment with Ptges inhibitors C118 and C934; n = 17 slices per condition for NBH; prion: n = 18 slices for DMSO; n = 20 slices for CP673451; n = 21 slices for CP673451 + C118 and CP673451 + C934. Data are presented as mean ± s.e.m. One-way ANOVA with Benjamini–Hochberg FDR adjustment for multiple comparisons: P < 0.0001 (NBH + DMSO versus prion + DMSO); P < 0.0001 (prion + DMSO versus prion + CP673451); P < 0.0001 (prion + CP673451 versus prion + CP673451 + C118); P = 0.0054 (prion + CP673451 versus prion + CP673451 + C934). c, Cox2 ablation (Cox2Luc) suppresses the acceleration of prion disease in NG2-glia-depleted (Pdgfrα^iDTR) mice. Median survival: 177 days for Pdgfrα^iDTR/WT mice; 184.5 days for Ctrl/WT mice; 199 days for Pdgfrα^iDTR/Cox2Luc and Ctrl/Cox2Luc mice. NG2 glia depletion was induced at 16 wpi; n = 10 mice for Ctrl/WT; n = 11 for Pdgfrα^iDTR/WT and Ctrl/Cox2Luc; n = 9 for Pdgfrα^iDTR/Cox2Luc. Log-rank test: P = 0.0049 (Ctrl/WT versus Pdgfrα^iDTR/WT); P = 0.0045 (Ctrl/WT versus Ctrl/Cox2Luc); P < 0.0001 (Pdgfrα^iDTR/WT versus Pdgfrα^iDTR/Cox2Luc); P = 0.6832 (Ctrl/Cox2Luc versus Pdgfrα^iDTR/Cox2Luc). d,e, Map2 immunofluorescence (d) and quantification (e) showing enhanced dendritic pathology in NG2-glia-depleted (Pdgfrα^iDTR) hippocampi of prion-infected mice, and its rescue by Cox2 ablation (Cox2Luc); n = 6 mice per group. Data are presented as mean ± s.e.m. One-way ANOVA with Benjamini–Hochberg FDR adjustment for multiple comparisons: P = 0.0003 (Ctrl/WT versus Pdgfrα^iDTR/WT); P = 0.0192 (Ctrl/WT versus Ctrl/Cox2Luc); P < 0.0001 (Pdgfrα^iDTR/WT versus Pdgfrα^iDTR/Cox2Luc); P = 0.8472 (Ctrl/Cox2Luc versus Pdgfrα^iDTR/Cox2Luc).

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