Figure 2

High fat diet (HFD) accelerates DNA damage in 6-month old mouse hippocampus and slows HR repair processes in wild-type and NHEJ APP/PSEN1 mice. (a) 16 weeks of HFD-feeding led to equivalent weight gain in both wild-type (WT, grey circles) and APP/PSEN1 (purple squares) mice. (b) Fewer NeuN-positive cells were observed in HFD-fed APP/PSEN1 mice compared to wild-types (t(5) = 4.41, p = 0.0069), and a strong trend toward decreased cell count was seen in HFD-fed wild-types compared to controls (dashed line, t(6) = 2.38, p = 0.054). (c) Greater apoptosis was seen in HFD-fed APP/PSEN1 mice compared to wild-types (t(6) = 7.236, p = 0.004), and Caspase3-positive cells were increased in HFD-fed wild-types compared to chow-fed controls (t(9) = 2.40, p = 0.040). (d) γ-H2AX-foci were more common in HFD-fed APP/PSEN1 (t(6) = 3.59, p = 0.012) compared to HFD wild-type mice, and increased in HFD wild-type mice compared to control wild-types (t(9) = 4.25, p = 0.0021). (e) RAD51-positive foci were decreased in HFD-fed wild-type mice compared to controls (t(4) = 6.47, p = 0.0029), but there was no further decrease in APP/PSEN1 mice. (f) Fewer 53BP1-positive foci were observed in APP/PSEN1 mice compared to wild-types on HFD (t(6) = 2.59, p = 0.041). Data are analyzed by separate 2-tailed t-tests within each comparison pair. *P < 0.05, ***P < 0.001 all HFD mice, APP/PSEN1 compared to wild-type as marked; ⁺P < 0.05, ⁺⁺P < 0.01 high fat diet-fed wild-type mice compared to age-matched control fed-wild-types (indicated by dashed line).