Fig. 5: Improvement of Aβ pathology and memory function in AppNL-F mice via enhancement of NEP activity by Dz treatment. | Molecular Psychiatry

Fig. 5: Improvement of Aβ pathology and memory function in AppNL-F mice via enhancement of NEP activity by Dz treatment.

From: Somatostatin-evoked Aβ catabolism in the brain: Mechanistic involvement of α-endosulfine-KATP channel pathway

Fig. 5

A NEP activity after treatment of co-cultured neurons for 24 h with different doses of diazoxide (Dz) (n = 9–10 for each group). B NEP activity in membrane fractions from anterior cortex (Ctx), posterior Ctx and hippocampus (Hip) of 4-month-old WT mice treated with or without Dz (n = 6 for each group). C, D. Immunoblotting of NEP in anterior Ctx of 4-month-old WT mice treated with or without Dz. Values indicated in the graph Values indicated in the graph show NEP band intensities normalized to that of β-actin (n = 4 for each group). E Aβ42 ELISA of GuHCl fractions from anterior Ctx and Hip of 4-month-old WT mice with or without Dz (Dz (–): n = 6, Dz (+): n = 7). F Aβ42 ELISA of GuHCl fractions from anterior Ctx and Hip of 6-month-old Mme KO mice with or without Dz (n = 8 for each group). G Freezing ratio of 18-month-old WT and AppNL-F mice treated with or without Dz (WT Dz (–): n = 12, WT Dz (+): n = 13, AppNL-F Dz (–): n = 10, AppNL-F Dz (+): n = 11). H, I Immunostaining of Aβ (Green) and NEP (Red) in Ctx, Subiculum and Molecular layer from 18-month-old AppNL-F with or without Dz (n = 7 for each group). Scale bar in cortical image = 500 µm and hippocampal image = 200 µm. J Aβ42 ELISA of GuHCl fractions from cortices and hippocampi of 18-month old AppNL-F with or without Dz (n = 8 for each group). K Immunostaining of NEP (Red) and VGAT (Green) in hippocampi from 18-month old AppNL-F with or without Dz. Scale bar is 100 µm in low-magnification image and 50 µm in high-magnification image. L. Statistical analysis of immunoreactivity of NEP (n = 5 for each group). LM: lacunosum-molecular layer, Omo: Outer molecular layer and MMo: middle molecular layer. M Statistical analysis of colocalized signals of NEP and VGAT (n = 5 for each group). In (A), the data represent the mean ± SEM. *P < 0.05, ***P < 0.001 (one-way ANOVA with Dunnett’s post-hoc test). In (B), (D), (E), (I), (J), (L), (M), the data represent the mean ± SEM. *P < 0.05, **P < 0.01, (Student’s t test). In (G) the data represent the mean ± SEM. On day 3, WT Dz (+) vs AppNL-F Dz (–) *P < 0.05. On day 4, WT Dz (–) vs AppNL-F Dz (–) *P < 0.05, WT Dz (+) vs AppNL-F Dz (–) **P < 0.01, AppNL-F Dz (–) vs AppNL-F Dz (+) *P < 0.05 (two-way ANOVA with Turkey’s multiple comparison test).

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