Figure 7.

AAV8-secGAA Administration Partially Normalizes Mitochondrial Stress Signaling in Skeletal Muscle

(A) Significant associations to 257 upstream transcriptional regulators were found for the set of 2,802 genes detected as differentially expressed in the comparison of PBS-Gaa^−/− versus PBS-Gaa^+/+ after IPA enrichment analyses. The circular plot represents a subset of 16 regulators involved in metabolic processes and a selection of their connected functions retrieved from IPA’s knowledge base with the “grow” function. Circular crown sectors, representing transcriptional regulators, are colored according to activation Z score. Red and blue colors indicate a higher activation state in PBS-Gaa^−/− or PBS-Gaa^+/+ mice, respectively. (B–D) 9-month-old mice were injected with an AAV8-secGAA (secGAA-Gaa^−/−) vector at a dose of 2 × 10¹² vg/kg. Gaa^+/+ (PBS-Gaa^+/+) and Gaa^−/− (PBS-Gaa^−/−) mice injected with PBS served as controls in the study. Animals were followed for 9 months after treatment (n = 3/4 per cohort). (B) ROS production measured in snap-frozen tissues by EPR spectroscopy. (C) Western blot analysis of triceps lysates using monoclonal antibody anti-AMPK. An anti-GAPDH antibody was used as a loading control. (D) Quantification of AMPK levels normalized to GAPDH levels from the corresponding western blot shown in (C). Statistical analysis: one-way ANOVA with Tukey’s post hoc. ∗∗p < 0.01. In all graphs, error bars represent the standard deviation of the mean.