Fig. 5: Cox2–Ptges inhibition diminishes prion neurotoxicity and decelerates prion disease.
a,b, NeuN immunofluorescence (a) and quantification (b) showing enhanced neurodegeneration in PGE2-treated compared with DMSO-treated and PGD2-treated Tga20 COCS after prion infection; n = 18 slices per condition. 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 + PGE2); P < 0.0001 (prion + PGE2 versus prion + PGD2); P = 0.8488 (prion + DMSO versus prion + PGD2). c,d, NeuN immunofluorescence (c) and quantification (d) showing diminished neurodegeneration in Tga20 COCS treated with Ptges inhibitors C118 and C934 compared with DMSO-treated Tga20 COCS after prion infection; n = 18 slices per condition. 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 + C118); P < 0.0001 (prion + DMSO versus prion + C934). e, Survival curves showing decelerated prion disease in Cox2 knockout (Cox2Luc) mice compared with littermate WT mice. Median survival: 186 days for control mice; 199 days for Cox2Luc mice; n = 9 mice per group. Log-rank test: P = 0.0024. f,g, Map2 immunofluorescence (f) and quantification (g) showing diminished dendritic pathology in the hippocampi of Cox2Luc mice after prion inoculation compared with littermate WT mice. Brain samples were collected at 21 wpi; n = 6 mice per group. Data are presented as mean ± s.e.m. Multiple unpaired t-tests (two-sided) with Benjamini–Hochberg FDR adjustment for multiple comparisons. NBH: P = 0.4270; Prion: P = 0.0033.
