Neuroprotective Effects of Ezetimibe versus Simvastatin in Alzheimer’s Induced Dementia: Perspectives from Female Rats. (P5.205)
Mahmoud Tawfik KhalafAllah, Mohamed Zalabia, Esraa Elsayed, Mohamed El‐Gamal, Mohamed Salama, Mohamed Ahdy, Mohamed Abdel kader Sobh, Wael M.Y. Mohamed · Neurology · 2016
Objective: To compare the potential neuroprotective effects of Ezetimibe versus Simvastatin in Alzheimer’s rat model and to explore how they modify Insulin Growth Factor 1 (IGF-1) signaling in the brain, which play a crucial role in learning and synaptic plasticity. Background: Among many theories, brain insulin resistance stood out in the last decade as a new approach for Alzheimer’s Disease (AD). Simvastatin and Ezetimibe can provide neuroprotection through their lipid lowering actions. However, their insulin-sensitizing actions can be as important as the former and has not yet been highlighted. Methods: Forty nine female Sprague-Dawely rats were allocated into seven equal groups: AD model (single unilateral ICV STZ, 3mg/kg), Sham group (single unilateral ICV 0.9 saline), Simvastatin Treated and Ezetimibe Treated groups received the same regimen as AD model plus simvastatin 10 mg/kg P.O (in the simvastatin-treated group) and Ezetimibe 10 mg/kg P.O (in the Ezetimibe-treated group) for 21 days. Simvastatin and Ezetimibe Control groups received simvastatin 10 mg/kg P.O and Ezetimibe 10 mg/kg P.O respectively for 21 days. Blank group was maintained on DW and standard diet. At 15th day, all animals were evaluated regarding spatial memory and learning through Morris Water Maze (MWM) and novel object recognition tests. On the 21st day, rats were scarified and brain sections were stained with Congo red and Golgi-Nissel stains and blotted against Anti-tau and Anti IGF-1 receptor antibodies. Results: Both Simvastatin and Ezetimibe showed protective effects through reducing amyloid plaques and tau aggregates and up regulating IGF-1 receptors in the hippocampus and the frontal cortex. Simvastatin treated group showed better performance than Ezetimibe treated group in MWM and novel object recognition tests. Conclusion: Both Simvastatin and Ezetimibe could protect against AD-induced dementia, evidenced by reducing amyloid and tau proteins through up regulation of IGF-1 receptors in the hippocampus and cerebral cortex.