Figure 2.

Captopril at a clinical dose exacerbates Aβ deposition in hAPPSw mice and induced neuronal damage at a high dose. A–C, systolic (SBP) and diastolic blood pressure (DBP) and heart rate of 17-month-old mice were indirectly measured with a tail-cuff apparatus. D, APP and APP CTF expression levels in the cortex were examined with Western blotting. E, thioflavin S staining of brain sections from 17-month-old captopril (capt)–treated hAPPSw mice (Tg2576). Low captopril indicates treatment with a clinical dose of captopril. F and G, number of thioflavin S–positive plaques (per section) in the hippocampus (F) and cortex (G) of the control, low captopril-treated, and high captopril-treated mice. Three or four sections were counted and averaged for each mouse. H, relative ACE activity in the serum of control, low captopril-treated, and high captopril-treated mice. I–Q, brain sections from control (I–K) and high captopril-treated mice (L–Q) were immunolabeled with NeuN antibody (green, I, L, and O) and Aβ42 antibody (red, J, M, and P), and imaged with confocal microscopy. Apoptotic neurons are indicated with arrowheads (O and Q). Diffuse Aβ42 deposition around neurons with nuclei was indicated with arrows (Q). R, number of Aβ42-positive plaques (per section) in the cortex of the control and high captopril-treated mice. S, thickness of lamina zonalis of the control and high captopril-treated mice. The data are the means ± S.E.; n = 6–12 mice in each group; male, 3–6; female, 3–6. *, p < 0.05; **, p < 0.01; ***, p < 0.001, by one-way ANOVA followed by Bonferroni–Dunn test versus the control diet mice. Scale bars indicate 500 μm in E and 20 μm in I–Q.