Abstract: It has been suggested that oxidative stress plays an important role in neural degeneration and Alzheimer's disease. Some studies have shown that metformin has some beneficial effects on the brain and reduces oxidative stress, while others reveal that metformin increases oxidative stress in diabetic patients. In this study acute and chronic effects of metformin and antioxidant protective effects of N-acetyl cysteine in Alzheimeric rats were investigated. Animals were divided into seven groups (n=8): Control, STZ, STZ + metformin (one, three and eleven weeks), STZ+ metformin (eleven weeks) +N-acetyl cysteine (eleven weeks) and N-acetyl cysteine (eleven weeks). ICV injections of saline (1μl/rat) or STZ (3mg/kg) and IP injections of Saline (1ml/kg), metformin (200mg/kg) and/or N-acetyl cysteine (100mg/kg) were done. Memory retrieval, CA1 neurons density and serums oxidative stress were investigated. STZ injections reduced memory retention, intact neurons and increased serum oxidative stress compared to the control (p<0/001). Metformin injection for one and three weeks (but not eleven weeks) improved the effects of STZ (p<0/001). Administration of N-acetylcysteine with metformin (eleven weeks) improved STZ bad effects (p<0/001). It seems that acute and chronic consumption of metformin have different effects on memory retrieval, CA1 neurons and serum oxidative stress factors in AD rats.
