The effect of metformin on learning and spatial memory in experimental model of Alzheimer’s disease induced by beta amyloid in rat

Background and Objective: Alzheimer Disease (AD) has a progressive and degenerative course on brain nerve cells due to deposition of beta amyloid and Tau protein. AD is associated with memory impairment with no eradicative cure. Metformin is a hypoglycemic drug that helps control diabetes mellitus type 2. Recently, neuroprotective and anti-inflammatory effect on nerve tissue and reductive effect on deposition of beta-amyloid and anti-oxidative stress effect of it has been proved. This study was done based on alzheimer modeling in rodents with injecting beta amyloid and to evaluate the effect of metformin treatment on its course.



Material and Methods: In this research study, 32 male rats were used. Rats were randomly divided into 4 groups. First group was healthy ones that treated with saline (sham), 2nd ones whom received metformin, 3rd group received normal saline and made alzheimeric (lesion) and last group was made alzheimeric and treated with metformin. The 2nd and 4th groups were treated with intraperitoneal metformin for 1 week before stereotaxic operation. For induction of AD, stereotaxic operation with injection of beta amyloid into hippocampus was made. After three weeks, for learning and memory assessment, passive-avoidance behaviour and Y-maze procedure were used.



Results: In comparison to sham group, lesion group had a lower average initial delay that this reduction was not statistically significant. The second lesion group had insignificant increase in the average initial delay, in comparison with other lesion group. The sham groups received the same amount of metformin had also non-significant reduction in initial delay time compared to the sham groups. Passive avoidance test in rats that had significantly decreased in the group with Alzheimer's disease compared to the sham group (p<0.01), although this decline is insignificant in the second group of Alzheimer model as compared to the sham group. In addition, the difference between the two groups with Alzheimer's disease was statistically significant (p<0.05).



Conclusion: The results indicate that chronic treatment with metformin increases the passive-avoidance test memory in shuttle box, but has no effect on the spatial memory in rats. Metformin is likely to be an appropriate candidate in the treatment of Alzheimer’s disease and the other different types of dementia in humans.