Chronic Cyclodextrin Treatment of Murine Niemann-Pick C Disease Ameliorates Neuronal Cholesterol and Glycosphingolipid Storage and Disease Progression (original) (raw)
Figure 6
Chronic CD treatment study in Npc2−/− mice.
(A) Average weight over time for untreated and CD-treated Npc2−/− and WT mice. Weights of untreated and CD-treated WTs were averaged for each gender as there was no significant difference between treatments (p<0.8125). (B) Survival of untreated and CD-treated Npc2−/− and WT mice. Median survival of Npc2−/− mice: no treatment, 144 days; CD (every other day), 248 days. CD-treated Npc2−/− mice lived significantly longer than untreated Npc2−/− mice (p<0.0108). (C) Filipin labeling of unesterified cholesterol in neocortex of untreated (end-stage, 145 days old) and CD-treated (start at P9; 150 days old) Npc2−/− mice revealed less cholesterol accumulation in the CD-treated mouse. (D) IHC of the same untreated and CD-treated Npc2−/− mice showed reduced GM2 labeling in the neocortex of the CD-treated mouse (also for GM3, not shown). (E) Biochemical analysis of ganglioside levels confirmed the reduction in GM2 and GM3 storage seen with IHC. Data from WT and mutant mice represent mean ± SD. Images taken at 20X (C) and 10X (D); scale bars 20 µm (C) and 50 µm (D).