Fig. 2

Felodipine in vivo dose-response experiments. a–c mRFP-GFP-LC3 transgenic mice (males and females, 6–7 weeks old) were injected i.p. with various doses of felodipine (1, 2, 5, 10 mg/kg body weight). a, b Treatment with 5 and 10 mg felodipine resulted in a statistically significant increase in autolysosomes and total vesicle number in the cerebral cortex with a similar trend observed in Purkinje cells. Autophagosome and autolysosome numbers are shown as mean +/− SEM; mean values of each vesicle type (autophagosome, autolysosome or total vesicles) for each dose of felodipine were compared with the mean value of same vesicle type to those in vehicle controls using one-sample, one-tailed unpaired t-test. Data shown was from 7 litters collected at different time-points (i.e., independent experiments), all values were normalised to mean autolysosome levels in the vehicle controls. c Representative images. Scale bar represents 10 µm in both cerebral cortex and Purkinje cells. d, e A six-week study was carried out on B6HD (N171–82Q) female mice. Mice were injected i.p. three times a week with 1, 2 or 5 mg/kg body weight of felodipine or vehicle control. Felodipine treatment resulted in a significant decrease in aggregates in the motor cortex (at 5 mg) and piriform cortex (2 and 5 mg). d Representative images of neuronal inclusions in piriform cortex and motor cortex of B6HD mice. Arrows indicate the neurons with huntingtin aggregates or inclusions, scale bar represents 10 µm. e Aggregate number was blind-counted in the motor cortex and piriform cortex. Data are presented as percentage of neurons with aggregates (mean +/− SEM) (n = 5 mice per group); analysed using one-way ANOVA with post hoc Dunnett’s multiple comparison test; exact p values for felodipine dose vs. control are shown