Abstract
Background and Objective: Alzheimer's Disease (AD) is a progressive neurodegenerative disorder characterized by loss of memory due to phosphorylation of tau protein, neurofibrillary lesions composed of the beta-amyloid peptide and aberrant oxidative stress. The objective is to study the combined neuroprotective effect of Selegiline with Piracetam against scopolamine and streptozotocin (STZ)-induced memory impairment in animals. Materials and Methods: This study was designed to investigate the synergistic neuroprotective effect of Selegiline with Piracetam by use of scopolamine and STZ model of memory impairment using the Morris water maze for the assessment of learning and memory. Various biochemical parameters such as acetylcholinesterase activity (AChE) as a marker of cholinergic activity, malondialdehyde (MDA) a marker of lipid peroxidation and glutathione (GSH) a marker of oxidative stress were estimated. Gene expression was also performed by RT-PCR and western blot test. Results: There were a significant decrease in MDA and AChE level and increase in GSH level as compared to the disease control group in Selegiline with Piracetam. In the present study, Bax and Bak mRNA (proapoptotic) were down-regulated, while Bcl-2 mRNA and protein which are antiapoptotic were up-regulated in Selegiline with Piracetam group opposite to the STZ group. Also, p53 expression in the given experiment was appreciably reduced in Selegiline with Piracetam group. Conclusion: The present study indicates that the administration of scopolamine and STZ cause a decline in memory function which is significantly improved by the treatment of selegiline with piracetam. The combined effect of selegiline with piracetam was found to be therapeutically more effective than the individual administration.