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

The use of AT1 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.

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 (3mg/kg) in days one and three. Treated groups received captopril (50mg/kg) and valsartan (30mg/kg) orally for 25days. 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.

Time of latency and error number for food searching was 73.4±15.5Sec and 11.8±1.2 in the control group respectively, induction of AD significantly increased these issues (216.2±57.9Sec, 16.2±2.9). 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 (46 and 86%) and error number (31 and 43%) and improved histopathological damages and increased BDNF mRNA.

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.