Fig. 2: NG2 glia depletion enhances prion neurotoxicity and accelerates prion disease.
a, NeuN and NG2 immunofluorescence showing prion-induced neurodegeneration in NG2-glia-depleted (CP673451) and NG2-glia-intact (DMSO) Tga20 COCS. b, Quantification of NG2 immunointensity and NeuN positive area shown in a. NeuN: n = 18 slices per condition. NG2: n = 19 slices for NBH + DMSO, NBH + CP673451 and prion + CP673451; n = 17 slices for prion + DMSO. Data are presented as mean ± s.e.m. One-way ANOVA with Benjamini–Hochberg FDR adjustment for multiple comparisons. NG2: P = 0.0002 (NBH + DMSO versus NBH + CP673451), P < 0.0001 (NBH + DMSO versus prion + DMSO), P < 0.0001 (prion + DMSO versus prion + CP673451); NeuN: P = 0.5603 (NBH + DMSO versus NBH + CP673451), P < 0.0001 (NBH + DMSO versus prion + DMSO), P < 0.0001 (prion + DMSO versus prion + CP673451). c, Survival curves showing accelerated prion disease in NG2-glia-depleted (PdgfrαiDTR) mice after prion inoculation. Median survival: 191 days for male PdgfrαiDTR mice; 205.5 days for male control mice; 174.5 days for female PdgfrαiDTR mice; 183 days for female control mice. Male: n = 10 for Ctrl; n = 7 for PdgfrαiDTR. Female: n = 11 for Ctrl; n = 6 for PdgfrαiDTR. Log-rank test: P = 0.0026 for male; P < 0.0001 for female. d, NG2 and Map2 immunofluorescence showing enhanced dendritic pathology in hippocampi of NG2-glia-depleted (PdgfrαiDTR) mice after prion inoculation. Arrowheads, pathologic dendrites with varicosities and fragmentation. NG2 glia depletion was induced at 16 wpi; brain samples were collected at 21 wpi. e, Quantification of NG2 immunointensity and Map2-positive area shown in d; n = 6 mice per group. Data are presented as mean ± s.e.m. Unpaired t-test (two-sided): P < 0.0008 for NG2; P = 0.0079 for Map2.
