Figure 4.
Metformin treatment rescues increased oxidative stress status in the brain and in the blood of RTT mice. (a) Blood ROS levels, measured as the intensity of formation of CP• by EPR, were significantly higher in RTT, sal mice compared to WT controls, confirming the occurrence of a pro-oxidant status in RTT mice. Metformin normalized this value in whole blood of RTT mice to the same level of WT controls. N = 3–4. One subject of the experimental group RTT, sal was identified as outlier and thus, excluded from the analysis. (b–c) Metformin treatment reduces the abnormal accumulation of protein 4-hydroxynonenal (HNE) adducts in RTT mouse hippocampus (c). Representative blot is shown in panel (b). N = 9–11. Data are mean ± SEM normalized for WT, sal. Statistical significance was calculated by two-way ANOVA, with Tukey’s post hoc test. * p < 0.05, ** p < 0.01. WT: wild-type mice; RTT: MeCP2-308 heterozygous female mice; sal: saline; met: metformin; HNE-adducts: 4-hydroxy-2-trans-nonenal protein bound.