Fig. 4: Intermittent MS1262 treatment increases frequency but not amplitude of sEPSCs in DG granule cells of 5xFAD mice without altering intrinsic excitability. | Nature Communications

Fig. 4: Intermittent MS1262 treatment increases frequency but not amplitude of sEPSCs in DG granule cells of 5xFAD mice without altering intrinsic excitability.

From: Development of a brain-penetrant G9a methylase inhibitor to target Alzheimer’s disease-associated proteopathology

Fig. 4: Intermittent MS1262 treatment increases frequency but not amplitude of sEPSCs in DG granule cells of 5xFAD mice without altering intrinsic excitability.The alternative text for this image may have been generated using AI.

A Quantification of membrane capacity between WT mice and 5xFAD mice treated with vehicle and MS1262 (n = 15/21/22 cells for WT/Vehicle/MS1262) ANOVA followed by Tukey’s test visualized as mean ± SEM. B Quantification of input resistance between WT mice and 5xFAD mice treated with vehicle and MS1262 (n = 15/21/22 cells for WT/Vehicle/MS1262) ANOVA followed by Tukey’s test visualized as mean ± SEM. C Quantification of resting membrane potential between WT mice and 5xFAD mice treated with vehicle and MS1262 (n = 15/21/22 cells for WT/Vehicle/MS1262) ANOVA followed by Tukey’s test visualized as mean ± SEM. D Mean ( ± SEM) number of action potential elicited in response to increasing step current from dentate granule cells of WT mice and 5xFAD mice injected with vehicle (black) or MS1262 (blue). (n = 15/21/22 cells for WT/Vehicle/ MS1262. ANOVA followed by Tukey’s test. E Representative traces of sEPSCs recorded from dentate granule cells derived from WT mice and 5xFAD mice injected chronically with vehicle (left) or MS1262 (right). F, G Cumulative probability (f) and average amplitude distribution (g) of sEPSCs (WT, n = 15 cells from 3 mice, 5xFAD-Vehicle, n = 16 cells from 3 mice; 5xFAD-MS1262, n = 15 cells from 3 mice) ANOVA followed by Tukey’s test visualized as mean ± SEM. H, I Cumulative probability distribution (h) and average frequency (i) of sEPSCs (WT, n = 15 cells from 3 mice, 5xFAD-Vehicle, n = 16 cells from 3 mice; 5xFAD-MS1262, n = 15 cells from 3 mice. P = 0.0004, Kruskal-Wallis test, Dunn’s test for multiple comparisons p < 0.0001 and p = .0453) visualized as mean ± SEM. J, K fEPSP slope (J) as measured as a percent of baseline and LTP visualized in a bar graph (k). (WT, n = 8 slices from 3 mice, 5xFAD-vehicle, n = 4 slices from 3 mice; 5xFAD-MS1262, n = 9 slices from 4 mice. ANOVA followed by Tukey’s test *p < 0.05, ****p < 0.0001 Data are visualized as mean ± SEM. (See also Data S3).

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