Dapagliflozin ameliorates Alzheimer’s disease in rats via stimulating the protective arm of renin angiotensin system and suppressing neuroinflammation

Figures

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  Fig. 1. Effect of DAPA treatment on cognitive functions of SCO-administered rats in NOR and Y-maze behavioral tests. Effect of DAPA on SCO-induced alterations of the percentage of A recognition index in novel object recognition (NOR) test, and B spontaneous alteration performance (SAP) in Y-maze test. SCO, scopolamine; DAPA, dapagliflozin. Each bar represents the mean ± SE of 8 rats per group. Statistical analysis was performed using one-way ANOVA followed by Student-Newman-Keuls multiple comparison test; *p < 0.05 versus control; #p < 0.05 versus SCO

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  Fig. 2. Effect of DAPA treatment on ACh and choline levels in hippocampal tissues of SCO-administered rats. Effect of DAPA on SCO-induced hippocampal alterations of A acetylcholine (ACh) level, and B choline level. SCO, scopolamine; DAPA, dapagliflozin. Each bar represents the mean ± SE of 8 rats per group. Statistical analysis was performed using one-way ANOVA followed by Student-Newman-Keuls multiple comparison test; *p < 0.05 versus control; #p < 0.05 versus SCO; $p < 0.05 versus DAPA

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  Fig. 3. Effect of DAPA treatment on inflammation in hippocampal tissues of SCO-administered rats. Effect of DAPA on SCO-induced hippocampal alterations of A nuclear factor kappa B (NF-κB) level, B interleukin-6 (IL-6) and C guanine nucleotide-binding protein alpha-3 (GNAI3) level. SCO, scopolamine; DAPA, dapagliflozin. Each bar represents the mean ± SE of 8 rats per group. Statistical analysis was performed using one-way ANOVA followed by Student-Newman-Keuls multiple comparison test; *p < 0.05 versus control; #p < 0.05 versus SCO; $p < 0.05 versus DAPA

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  Fig. 4. Effect of DAPA treatment on apoptosis in hippocampal tissues of SCO-administered rats. Effect of DAPA on SCO-induced hippocampal alterations of A cytochrome-c (CYC) level and B caspase-3 (Casp-3) level. SCO, scopolamine; DAPA, dapagliflozin. Each bar represents the mean ± SE of 8 rats per group. Statistical analysis was performed using one-way ANOVA followed by Student-Newman-Keuls multiple comparison test; *p < 0.05 versus control; #p < 0.05 versus SCO; $p < 0.05 versus DAPA

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  Fig. 5. Effect of DAPA treatment on RAS protective arm components in hippocampal tissues of SCO-administered rats. Effect of DAPA on SCO-induced hippocampal alterations of A angiotensin converting enzyme 2 (ACE2) level, B angiotensin 1–7 (Ang 1–7) level, and C Mas receptor (MAS1) expression. SCO, scopolamine; DAPA, dapagliflozin. Each bar represents the mean ± SE of 8 rats per group. Statistical analysis was performed using one-way ANOVA followed by Student-Newman-Keuls multiple comparison test; *p < 0.05 versus control; #p < 0.05 versus SCO; $p < 0.05 versus DAPA

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  Fig. 6. Effect of DAPA treatment on RAS classical arm components in hippocampal tissues of SCO-administered rats. Effect of DAPA on SCO-induced hippocampal alterations of A angiotensin converting enzyme (ACE) expression, B angiotensin II (Ang II) level, and C angiotensin II type 1 receptor (AT1) level. SCO, scopolamine; DAPA, dapagliflozin. Each bar represents the mean ± SE of 8 rats per group. Statistical analysis was performed using one-way ANOVA followed by Student-Newman-Keuls multiple comparison test; *p < 0.05 versus control; #p < 0.05 versus SCO; $p < 0.05 versus DAPA

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  Fig. 7. Effect of DAPA treatment on PKA and PI3K levels in hippocampal tissues of SCO-administered rats. Effect of DAPA on SCO-induced hippocampal alterations of A protein kinase A (PKA) level, and B phosphoinositide 3-kinase (PI3K) level. SCO, scopolamine; DAPA, dapagliflozin. Each bar represents the mean ± SE of 8 rats per group. Statistical analysis was performed using one-way ANOVA followed by Student-Newman-Keuls multiple comparison test; *p < 0.05 versus control; #p < 0.05 versus SCO; $p < 0.05 versus DAPA

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  Fig. 8. Effect of DAPA treatment on histopathological alterations in hippocampal tissues of SCO-administered rats. Photomicrographs of hippocampal rat tissue (H&E, x400). A Control rat demonstrating normal histological structure. B SCO-administered rats showing loss of pyramidal cells, vacuolation (star) and pyknotic neurons (curved arrow). C DAPA-only treated rat showing unchanged histological structure from the control rat. D SCO + DAPA-treated rat revealing mild pathological alterations of the pyramidal cells and few scattered pyknotic neurons