Metformin, a calorie restriction mimetic for the treatment of Alzheimer’s disease: A preclinical investigation

Background Laboratory experiments have repeatedly demonstrated that organisms can live longer, healthier lives by reducing their calorie intake, with the implication that the same might be true for humans. Therefore, calorie restriction mimetics have generated lot of interest in the treatment of age related disorders. Metformin was shown to have caloric restriction-related longevity benefit mediated by the activation of AMPK in C. elegans. Metformin also has beneficial effect on other aspects of the aging process such as a decrease in age-related disease incidence. Based on this background metformin was evaluated in the current preclinical investigation as a potential treatment approach for AD. Method Rats were treated with Aluminium chloride (AlCl3; 10 mg/kg, i.p.) for 21 days for induction of oxidative stress leading to neurodegeneration. Animals were treated with metformin (50 and 100 mg/kg, p.o.) in parallel to AlCl3. Control group of rats received either saline alone or AlCl3 alone. Animals were subjected for evaluation in radial arm maze followed by assessments of biomarkers in brain (Malondialdehyde, glutathione, BDNF) and lipid parameters in plasma. Result Impaired cognitive abilities were observed in rats treated with AlCl3 alone; however metformin produced significant decrease in total errors and increased % choice accuracy. Similarly, oxidative stress evaluated through the measurement of malondialdehyde was increased in animals treated with AlCl3, and metformin produced decrease in oxidative stress marker and increase in BDNF expression. Conclusion Results from the current studies indicate that calorie restriction mimetics might have potential beneficial effects in the management of AD through improvement of anti-aging properties.