Fig. 1
SUL-138 treatment rescues memory and LTP deficits in APP/PS1 mice. A SUL-138 increases mitochondrial electron transport chain complexes I (type I NADH dehydrogenase) and IV (cytochrome c oxidase) activity and efficiency, decreasing reactive oxygen species (ROS) and increasing ATP levels [23]. B Wildtype (WT) and APP/PS1 mice were treated with vehicle- or SUL-138-containing food pellets from 3 to 6 months of age after which conditioned fear memory or long-term potentiation (LTP) was measured and amyloid plaques were detected using immunohistochemistry (IHC) in APP/PS1 mice. C Representative pre- (black) and post-tetanus (orange/purple) fEPSP traces for control and SUL-138-treated WT and APP/PS1 mice. D LTP was measured as the fEPSP slope as percentage of baseline for control (open dot) and SUL-138-treated (solid dot) WT (orange) and APP/PS1 (purple) mice (Student’s t-test, *p ≤ 0.05). E LTP maintenance at 30–60 min after tetanus was significantly higher in SUL-138-treated compared to control mice in both WT (121.00 ± 4.67 vs 110.90 ± 2.24) and APP/PS1 (110.90 ± 5.74 vs 123.40 ± 3.99) mice (WT VEH n = 10, WT SUL n = 13, APP VEH n = 8 and APP SUL n = 10; Student’s t-test, *p ≤ 0.05). F Freezing levels after re-exposure to the context were significantly lower in vehicle-treated APP/PS1 mice compared to vehicle-treated WT mice (13.85 ± 2.54 vs 23.78 ± 2.49; WT VEH n = 22, APP VEH n = 18; one-way ANOVA, post hoc Fisher’s LSD; ## p ≤ 0.01), confirming a memory impairment in APP/PS1 mice. SUL-138 treatment increased memory in WT mice (38.28 ± 3.98 vs 23.78 ± 2.49; WT SUL n = 23; one-way ANOVA, post-hoc Fisher’s LSD, **p ≤ 0.01) and rescued memory in APP/PS1 mice up to WT levels (13.85 ± 2.54 vs 25.04 ± 3.80; APP SUL n = 21; one-way ANOVA, post hoc Fisher’s LSD, *p ≤ 0.05). Little to no freezing was observed in the novel context (NC). Plaque number (G) and plaque size (H) in the hippocampus (2 slices per animal, mean of 4 hippocampi) were significantly lower in SUL-138-treated APP/PS1 mice compared to vehicle-treated APP/PS1 mice (n = 5; 2.800 ± 0.8456 vs 6.100 ± 1.719 and 0.028 ± 0.0028 vs 0.040 ± 0.0014 respectively; Student’s t-test, **p ≤ 0.01, *p ≤ 0.05)