Fig. 8: DSBs depend on base excision of oxidized bases in vivo.

a Schematic diagram of DSB formation from two “in trans” SSBs leading to DSBs after excision of oxidized bases during BER. b Diagram of functional parts of the XJB-5-31 ROS inhibitor and its chemical structure. The red ball represents the tempol antioxidant (red) (red hatched box), which is fused to a mitochondria-targeted carrier peptide (black) (black hatched box)^60,61,62,63. The target carrier peptide is based on the Gramicidin S, an antibiotic that targets the mitochondrial membrane directly. c Single-cell quantification of DSBs in brain tissue sections from vehicle (gray) (n = 3) or XJB-5-131 treated (black) (n = 3) male C57BL/6J mice as measured by IF signal intensity of cells that co-stain with NeuN and γH2AX. In each tissue section, the DSB marker γH2AX was quantified in 50 randomly selected NeuN positive neurons from CBL, STR, CTX, and HIP of (n = 3) treated male C57BL/6J mice of 80–90 weeks (black) and n = 3 vehicle treated control mice of comparable age (gray). The regional-specific comparisons of DSB marker level were evaluated using a one-way ANOVA. Treated mice were characterized by a statistically significant reduction in γH2AX signal intensity relative to vehicle treated animals, ****P < 0.00001.