Exercise Normalized the Hippocampal Renin-Angiotensin System and Restored Spatial Memory Function, Neurogenesis, and Blood-Brain Barrier Permeability in the 2K1C-Hypertensive Mouse

Figures

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  Figure 1. Exercise improved the 2K1C-hypertension-induced spatial memory impairment. (A) Maze schematic with swimming trajectory for different groups of mice. Red circle: removed escape platform. (B) Upper: Acquisition escape latency to find a hidden platform by day in the training trials. Lower: The time in target quadrant for hidden platform removed probe test. The averaged data and s.d. are plotted. The statistical analysis was performed by one-way ANOVA and Holm-Sidak’s multiple comparisons. The sample sizes for sham, 2K1C, Sham-Ex, and 2K1C-EX are 11, 10, 10, and seven, respectively. **: p < 0.01, ***: p < 0.001, ****: p < 0.0001.

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  Figure 2. Exercise prevents the 2K1C-hypertension-induced AHN impairment. The immunohistochemistry micrographs for (A) Ki67+ neuronal stem cells and (B) DCX+ neuronal progenitor cells. The averaged data and s.d. are plotted. The statistical analysis was performed by one-way ANOVA and Holm-Sidak’s multiple comparisons. The sample sizes are seven for each group. *: p < 0.05. Scale bar, 300 μm.

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  Figure 3. Exercise prevents the 2K1C-hypertension-induced hippocampus neuronal cell pyknosis. (A) The H&E staining micrographs for CA1 (CA) and dentate gyrus (DG) of hippocampal. (B) The quantitative result for pyknosis cell density in the CA and DG. The averaged data and s.d. are plotted. The statistical analysis was performed by one-way ANOVA and Holm-Sidak’s multiple comparisons. The sample sizes are seven for each group. *: p < 0.05 **: p < 0.01, ***: p < 0.001. Scale bar, 300 μm.

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  Figure 4. Exercise restores the 2K1C-hypertensive mouse model plasma angiotensin II level without decreasing the blood pressure. (A) The plasma Ang II level was measured by ELISA. The statistical analysis was performed by one-way ANOVA and Holm-Sidak’s multiple comparisons. The averaged data and s.d. are plotted. The sample sizes are seven for each group. ***: p < 0.001, ****: p < 0.0001. (B) The systolic blood pressure was measured before and after surgery and after exercise training. The statistical analysis was performed by two-way ANOVA and Holm-Sidak’s multiple comparisons. The averaged data and s.d. are plotted. The sample sizes for sham, 2K1C, Sham-Ex, and 2K1C-EX are 11, 10, 10, and 7, respectively. *: p < 0.05, ***: p < 0.001, ****: p < 0.0001.

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  Figure 5. Exercise downregulates the 2K1C-hypertensive mouse model hippocampus RAS. (A) Representative immunoblots for each group of hippocampus tissue of the mice. (B) The quantitative result for protein level of Ang II, Angiotensinogen type I receptor (AGTR1), and Angiotensinogen type II receptor (AGTR2). The statistical analysis was performed by one-way ANOVA and Holm-Sidak’s multiple comparisons. The averaged data and s.d. are plotted. The sample sizes are seven for each group. **: p < 0.01, ***: p < 0.001, ****: p < 0.0001.

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  Figure 6. Exercise prevents the 2K1C-hypertensive mouse model hippocampus BBB leakage. (A) The immunohistochemistry micrographs for the mouse-IgG2a staining in the hippocampus CA1 and dentate gyrus (DG). (B) The quantitative result for IgG2a antibody level in the hippocampus CA1 and DG. (C) The plasma S100B level was measured by ELISA. The statistical analysis was performed by one-way ANOVA and Holm-Sidak’s multiple comparisons. The averaged data and s.d. are plotted. The sample sizes are seven for each group. *: p < 0.05, **: p < 0.01, ****: p < 0.0001. Scale bar, 100 μm.