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Fig. 8 | Molecular Neurodegeneration

Fig. 8

From: NMNAT2 supports vesicular glycolysis via NAD homeostasis to fuel fast axonal transport

Fig. 8

SARM1 knockdown restores APP axonal transport in NMNAT2 KO neurons (A1, B1, C1) Experimental timeline. (A2, B2, C2) Percentages of APP vesicles moving anterogradely, retrogradely, or staying stationary in distal axons of ctrl and KO neurons following the treatments indicated in A1, B1, and C1, respectively. Numbers of neurons imaged and statistics: (A2) 27 ctrl + ctrl ASO, 31 KO + ctrl ASO, 29 ctrl + SARM1 ASO, and 33 KO + SARM1 ASO, *p = 0.0286, #p = 0.018, **p = 0.0069. (B2) 20 ctrl + ctrl ASO, 22 KO + ctrl ASO, 14 ctrl + SARM1 ASO, and 26 KO + SARM1 ASO. (C2) 25 ctrl + ctrl ASO, 31 KO + ctrl ASO, 22 ctrl + SARM1 ASO, and 26 KO + SARM1 ASO, ###p = 0.0006. Significant comparison to KO + ctrl ASO group was labeled with #. (A3-4, B3-4, C3-4) Velocity of antero- and retrograde transport in distal axons of ctrl and KO neurons following the treatments indicated in (A1, B1, C1), respectively. (A3-4) 26-27 ctrl + ctrl ASO, 26-27 KO + ctrl ASO, 29 ctrl + SARM1 ASO, and 32-33 KO + SARM1 ASO. (B3-4) 20 ctrl + ctrl ASO, 14-16 KO + ctrl ASO, 14 ctrl + SARM1 ASO, and 20-22 KO + SARM1 ASO, (ctrl + SARM1 ASO vs KO + SARM1 ASO) **p = 0.0049, (ctrl + ctrl ASO vs KO + ctrl ASO) **p = 0.0022. (C3-4) 24-25 ctrl + ctrl ASO, 16-19 KO + ctrl ASO, 20-22 ctrl + SARM1 ASO, and 22-26 KO + SARM1 ASO, **p = 0.001. One-way or two-way ANOVA with Tukey's multiple comparisons test and Kruskal-Wallis test with Dunn's multiple comparisons test were used; see details in supplemented Excel. All above data represent mean ± SEM, ****p < 0.0001, ####p < 0.0001. Numbers of independent culture experiments are listed in Sup. Table

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