Fig. 3: 4-HMA improves PC function and behavioural phenotypes of Hpdl−/− mice.
From: Coenzyme Q headgroup intermediates can ameliorate a mitochondrial encephalopathy
a, Electron flow in cerebellar mitochondria from P9 Hpdl+/+, Hpdl+/− and Hpdl−/− pups as well as P9 4-HMA-treated Hpdl−/− pups. Electron flow through complexes I and II is impaired in Hpdl−/− mice and is restored by 4-HMA treatment. There was a non-statistically significant decrease in electron flow, rescued by 4-HMA, through complex IV. n = 5 animals for all groups. OCR, oxygen consumption rate. b, Patch-clamping of PCs in brain slices from P8–10 pups increases input resistance (Ri) and decreases membrane capacitance (Cm) in PCs from Hpdl−/− pups relative to PCs from Hpdl+/+ and Hpdl+/− pups. (Hpdl+/+, n = 20; Hpdl+/−,, n = 20; Hpdl−/−, n = 20; 4-HMA-treated Hpdl−/−, n = 18). c, 4-HMA supplementation restores input resistance and membrane capacitance of PCs from Hpdl−/− pups to levels comparable to those in Hpdl+/+ and Hpdl+/− pups on P17–19. (Hpdl+/+, n = 13; Hpdl+/−, n = 10; 4-HMA-treated Hpdl−/−, n = 12). d, 4-HMA-treated 8–10-week-old Hpdl−/− mice have reduced gait regularity relative to Hpdl+/+ and Hpdl+/− mice. There were no differences in gait speed between the groups. e,f, 4-HMA-treated 8–10-week-old Hpdl−/− mice have similar performance to Hpdl+/+ and Hpdl+/− mice in the pole test (e) and the transverse beam test (f). g, Forelimb grip strength (left) is decreased in 8–10-week-old Hpdl+/− and 4-HMA-treated Hpdl−/− mice relative to Hpdl+/+ mice. All-limb grip strength (right) is similar in all groups. For behavioural tests, data from male mice (n: Hpdl+/+ = 4, Hpdl+/− = 5, 4-HMA-treated Hpdl−/− = 4) are plotted as triangles. Data from female mice (n: Hpdl+/+ = 4, Hpdl+/− = 2, 4-HMA-treated Hpdl−/− = 5) are plotted as circles. Behavioural data do not include untreated Hpdl−/− mice. Data are mean ± s.e.m. as well as raw data. For box-and-whisker plots, the centre is the median, the box bounds are the 25th to 75th percentiles and whiskers indicate minimum to maximum. Significance was tested by two-way ANOVA with Tukey’s post hoc test.
