Protective Effects of Captopril and Valsartan on Memory Function and Gene Expression of Brain-Derived Neurotrophic Factor (BDNF) in Experimental Model of Alzheimer’s Disease in Rats

Background and Objective: The use of AT۱ and ACE inhibitors, as antihypertensive drugs, improves memory function in the elderly people with hypertension and vulnerable to Alzheimer’s disease (AD). Therefore, the aim of this study was to evaluate effects of oral administration of Captopril and Valsartan on memory function and expression of brain-derived neurotrophic factor (BDNF) in experimental model of AD in rats. Materials and Methods: Forty adult male Wistar rats were assigned to five groups Control, Vehicle, Alzheimer, Captopril and Valsartan treated groups. AD in the Alzheimer and treated groups was induced using bilateral i.c.v. injection of streptozotocin (۳mg/kg) in days one and three. Treated groups received captopril (۵۰mg/kg) and valsartan (۳۰mg/kg) orally for ۲۵days. At the end of the experiment, memory function was tested using T-Maze and gene expression of BDNF was assessed by RT-PCR technique. Finally, histopathological damages were evaluated using H&E and toluidine blue staining methods. Results: Time of latency and error number for food searching was ۷۳.۴±۱۵.۵Sec and ۱۱.۸±۱.۲ in the control group respectively, induction of AD significantly increased these issues (۲۱۶.۲±۵۷.۹Sec, ۱۶.۲±۲.۹). Histopathological damages (necrotic neurons and tissue vacuolization) along with reduction of BDNF mRNA were obviously observed in rats of the Alzheimer group. Captopril and valsartan treatment led to a decrease in the time of latency (۴۶ and ۸۶%) and error number (۳۱ and ۴۳%) and improved histopathological damages and increased BDNF mRNA. Conclusion: Our findings indicated that inhibition of central renin-angiotensin improves memory function and neuronal damages during AD disease. It appears that activation of this system inhibits gene expression of BDNF.

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Key words: Renin-angiotensin System ، Captopril ، Valsartan ، BDNF ، Alzheimer’s Disease