Metformin mitigates amyloid β1-40-induced cognitive decline via attenuation of oxidative/nitrosative stress and neuroinflammation

Metformin is an antidiabetic medicine widely used for management of type 2 diabetes with neuroprotective effects and promising potential to attenuate cognitive impairment. The efficacy of metformin in attenuation of Alzheimer's disease (AD) pathology has not been well-documented. Thus, this study was designed to assess protective effect of metformin against A beta(1-40)-instigared cognitive impairment. After intra-CA1 microinjection of aggregated A beta(1-40), rats received oral metformin (50 and/or 200 mg/kg/day) for two weeks. Cognition function was analyzed in various behavioral tasks besides measurement of hippocampal oxidative stress, apoptosis, and inflammation along with H&E staining and 3-nitrotyrosine (3-NT) immunohistochemistry. Obtained data showed significant improvement of discrimination score in novel object recognition test, higher alternation score in Y maze, greater latency in passive avoidance task, and lower working and reference memory errors in radial arm maze in metformin-treated A beta-injured group. Moreover, metformin treatment attenuated hippocampal levels of nitrite, MDA, protein carbonyl, ROS, TNF alpha, GFAP, DNA fragmentation intensity, caspase 3 activity, AChE activity, and increased SOD activity and level of IL-10 as an anti-inflammatory factor. In addition, metformin treatment was associated with lower CA1 neuronal loss and it also decreased intensity of 3-NT immunoreactivity as an indicator of nitrosative stress. Taken together, obtained findings showed neuroprotective and anti-dementia property of metformin in male rats and this may have potential benefit in attenuation of cognitive decline and related complications in patients with neurodegenerative disorders such as AD besides diabetes mellitus.

Automated summary

This study aimed to evaluate the protective effect of metformin against A beta(1-40)-induced cognitive impairment. The results showed that metformin improved cognitive function in rats and attenuated hippocampal damage such as oxidative stress, apoptosis, and inflammation. This study reveals the neuroprotective and anti-dementia properties of metformin.