Metformin Mitigates Memory Impairment of Diabetic Mice through Modulation of Plasma Pro-inflammatory Cytokines and Aβ1-42 Levels

Abstract Experimental and clinical studies reported that type 2 diabetes mellitus (T2DM) is associated with cognitive dysfunction and promotes the onset of dementia. Metformin is an antihyperglycemic drug used for the treatment of T2DM. A growing number of evidence revealed neuroprotective, antioxidant, and anti-inflammation effects exerted by metformin. The present study aimed to investigate the effect of metformin on cognitive function, systemic proinflammatory cytokines and amyloid-beta 1-42 (Aβ1-42) which is a pathological hallmark of Alzheimer’s disease (AD) in diabetic mice. C57BL/6N mice were divided into the following experimental groups: normal control group (NC); diabetes mellitus group (DM) induced by a high-fat diet combined with streptozotocin (STZ) injection; diabetes mellitus treated with metformin 100 mg/kg (DM+Met). Cognitive performance was evaluated by the novel object recognition test (NORT). Systemic proinflammatory cytokines and Aβ1-42 were assessed by the enzyme-linked immunosorbant assay (ELISA) test. We found that diabetic mice exhibited cognitive impairment in NORT whereas the treatment with metformin restored the cognitive function of diabetic mice. Moreover, diabetic mice presented an increase in plasma IL-6 and TNF-α levels while Aβ1-42 was decreased when compared to NC mice. Nevertheless, the administration of metformin allowed the levels of plasma IL-6, TNF-α, and Aβ1-42 to normalize in diabetic mice. Taken together, our findings suggest that metformin improves the cognitive function of diabetic mice possibly via the modulation of plasma pro-inflammatory cytokines and Aβ1-42 levels. Metformin may potentially be used as a therapeutic agent for patients with T2DM who show cognitive deficits. Keywords: Diabetes mellitus, Cognitive impairments, Pro-inflammatory cytokines, Amyloid-beta, Metformin