Figure 9.

SB treatment recovers PDH function, energy metabolism, and motor coordination in YAC128 mice. Histone 3 acetylation (AcH3; n = 6/7; A), PDH E1 alpha subunit phosphorylation at Ser232 (n = 5; B), relative mRNA expression of PDK1–3 (n = 6/8; C), ATP/ADP ratio (n = 4/5; D), and energy charge (n = 4/5; E) were analyzed in cortical brain fractions from YAC128 (HD53 line) and wild-type mice after treatment with saline (control group) or SB (1 mg/kg/d) for 28 d. Behavioral analysis was performed in a rotarod apparatus in a fixed speed (5 rpm; motor learning; F) and in accelerated speed (from 5 to 40 rpm; motor coordination; G) (n = 9/13) and the latency to fall off was recorded, as indicated in the Materials and Methods. Data are shown as the mean ± SEM of the indicated animals from each treatment. Statistical analysis was performed by two-way ANOVA and revealed a significant interaction between genotype and SB treatment shown in B (F_{(1, 31)} = 6.113, p = 0.0191), D (F_{(1, 14)} = 5.627, p = 0.0326), and E (F_{(1, 14)} = 9.536, p = 0.0086). A strong significant effect of SB treatment is shown in A (F_{(1, 31)} = 25.22, p < 0.0001), B (F_{(1, 31)} = 16.08, p = 0.0004), and G (F_{(1, 58)} = 16,90, p = 0.0001). In G, there is a significant effect of the genotype (F_{(1, 67)} = 14,66, p = 0.0003). Statistical significance: *p < 0.05, **p < 0.01, ***p < 0.001, and ****p < 0.0001 compared with wild-type saline-treated group; ^##p < 0.01, ^###p < 0.001, and ^####p < 0.0001 compared with the respective saline-treated group; and ^&&&p < 0.001 between the three cohorts of mice throughout trials 2 to 4 by two-way ANOVA followed by Bonferroni post test and by Student's t test: ^tp < 0.05 (in C).