Insulin deficiency or resistance can promote dementia and hallmarks of Alzheimer's disease (AD). The formation of neurofibrillary tangles of p-TAU protein, extracellular Aβ plaques, and neuronal loss is related to the switching off insulin signaling in cognition brain areas. Metformin is a biguanide antihyperglycemic drug used worldwide for the treatment of type 2 diabetes. Some studies have demonstrated that metformin exerts neuroprotective, anti-inflammatory, anti-oxidant, and nootropic effects. This study aimed to evaluate metformin's effects on long-term memory and p-Tau and amyloid β modulation, which are hallmarks of AD in diabetic mice. Swiss Webster mice were distributed in the following experimental groups: control; treated with streptozotocin (STZ) that is an agent toxic to the insulin-producing beta cells; STZ + metformin 200 mg/kg (M200). STZ mice showed significant augmentation of time spent to reach the target box in the Barnes maze, while M200 mice showed a significant time reduction. Moreover, the M200 group showed reduced GFAP immunoreactivity in hippocampal dentate gyrus and CA1 compared with the STZ group. STZ mice showed high p-Tau levels, reduced p-CREB, and accumulation of β-amyloid (Aβ) plaque in hippocampal areas and corpus callosum. In contrast, all these changes were reversed in the M200 group. Protein expressions of p-Tau, p-ERK, pGSK3, iNOS, nNOS, PARP, Cytochrome c, caspase 3, and GluN2A were increased in the parietal cortex of STZ mice and significantly counteracted in M200 mice. Moreover, M200 mice also showed significantly high levels of eNOS, AMPK, and p-AKT expression. In conclusion, metformin improved spatial memory in diabetic mice, which can be associated with reducing p-Tau and β-amyloid (Aβ) plaque load and inhibition of neuronal death.

胰岛素缺乏或抵抗可促进痴呆和阿尔茨海默病 (AD) 的标志。p-TAU 蛋白的神经原纤维缠结、细胞外 Aβ 斑块和神经元丢失的形成与关闭认知脑区的胰岛素信号传导有关。二甲双胍是一种双胍类抗高血糖药物，在全球范围内用于治疗 2 型糖尿病。一些研究表明，二甲双胍具有神经保护、抗炎、抗氧化和促智作用。本研究旨在评估二甲双胍对长期记忆和 p-Tau 和淀粉样蛋白 β 调节的影响，这些是糖尿病小鼠 AD 的标志。瑞士韦伯斯特小鼠分布在以下实验组中：对照组；用链脲佐菌素 (STZ) 治疗，该药物对产生胰岛素的 β 细胞有毒；STZ + 二甲双胍 200 mg/kg (M200)。STZ 小鼠在巴恩斯迷宫中到达目标框的时间显着增加，而 M200 小鼠的时间显着减少。此外，与 STZ 组相比，M200 组在海马齿状回和 CA1 中的 GFAP 免疫反应性降低。STZ 小鼠在海马区和胼胝体中显示出高 p-Tau 水平、减少的 p-CREB ​​和 β-淀粉样蛋白 (Aβ) 斑块的积累。相比之下，所有这些变化在 M200 组中都得到了逆转。STZ 小鼠顶叶皮质中 p-Tau、p-ERK、pGSK3、iNOS、nNOS、PARP、细胞色素 c、caspase 3 和 GluN2A 的蛋白质表达增加，而在 M200 小鼠中则显着抵消。此外，M200 小鼠还表现出显着高水平的 eNOS、AMPK 和 p-AKT 表达。综上所述，