The effects of perindopril on cognitive impairment induced by d-galactose and aluminum trichloride via inhibition of acetylcholinesterase activity and oxidative stress

Abstract

Preclinical and clinical studies indicate involvement of renin angiotensin system (RAS) in memory functions. However, exact role of RAS in cognition is still ambiguous. The present study investigated the effects of perindopril on dementia of Alzheimer's type induced by d-galactose (d-gal) and aluminum trichloride (AlCl3). Perindopril, an angiotensin converting enzyme inhibitor, was administered intragastrically (0.5mg/kg/day) for 60days after mice were given d-gal (150mg/kg/day) and AlCl3 (10mg/kg/day) intraperitoneally for 90days. Then, memory function was evaluated by Morris water maze test. The biochemical studies were conducted in cerebral cortex and hippocampus of mouse brain after the behavioral studies. d-Gal and AlCl3 caused significant memory impairment along with significant elevation of acetylcholinesterase (AChE) activity in cerebral cortex and hippocampus. Further, a significant reduction of superoxide dismutases (SOD) and glutathione peroxidase (GSH-Px) activities, and elevation of malondialdehyde (MDA) level in cerebral cortex and hippocampus were observed. Perindopril not only improved cognitive impairment but also restored the elevation of AChE activity induced by d-gal and AlCl3. In addition, perindopril significantly increased SOD and GSH-Px activities, reduced MDA level in cerebral cortex and hippocampus. Taken together, the above findings indicate that perindopril improves learning and memorizing probably by restoring cholinergic function and attenuating oxidative damage.

Keywords: Acetylcholinesterase; Alzheimer's disease; Cognitive impairment; Oxidative stress; Perindopril.