Balikesir University, Faculty of Medicine, Department of Medical Pharmacology, Cagis Campus, Balikesir, Turkey.
Kocaeli University, Faculty of Medicine, Department of Medical Pharmacology, Umuttepe Campus, Kocaeli, Turkey.
Pharmacol Rep. 2019 Oct;71(5):818-825. doi: 10.1016/j.pharep.2019.04.015. Epub 2019 Apr 21.
Alzheimer's disease (AD) is the most common neurodegenerative disease in the world. One of the most commonly prescribed oral antidiabetic drug, metformin, has been shown to have beneficial effects on restoring impaired cognitive function. In the present study, we investigated the effects of metformin on spatial memory in terms of alleviating scopolamine-induced learning and memory impairments in rats by using the Morris water maze (MWM) test and the modified elevated plus-maze (mEPM) test. Furthermore, we investigated the possible mechanisms of action of metformin in preventing cognitive dysfunction.
Male Wistar rats received metformin (50, 100, or 200 mg/kg/day) via gavage feeding for three weeks. Scopolamine was administered intraperitoneally before the probe step of the MWM test or the acquisition session of the mEPM test.
The learning and memory impairment induced by scopolamine was reversed by metformin. In addition, metformin improved the level of phosphorylated AMP-activated protein kinase and cAMP responsive element binding protein. However, metformin pretreatment had no impact on inhibiting the scopolamine-induced changes in acetylcholine levels. Furthermore, metformin exerted its antioxidant effect by significantly reversing scopolamine-induced changes in malondialdehyde, total antioxidant status, and superoxide dismutase levels in the hippocampus.
Our results indicate that one of the most commonly used antidiabetic drug, metformin, has the potential to prevent the development of dementia and be a novel therapeutic drug for the amelioration of cognitive dysfunction in AD.
阿尔茨海默病（AD）是世界上最常见的神经退行性疾病。二甲双胍是最常被开的口服降糖药之一，已被证明对恢复受损的认知功能有有益作用。在本研究中，我们通过 Morris 水迷宫（MWM）测试和改良高架十字迷宫（mEPM）测试，研究了二甲双胍对空间记忆的影响，以缓解东莨菪碱引起的大鼠学习和记忆障碍。此外，我们还研究了二甲双胍预防认知功能障碍的可能作用机制。
雄性 Wistar 大鼠通过灌胃给予二甲双胍（50、100 或 200mg/kg/天），连续 3 周。东莨菪碱在 MWM 测试的探测步或 mEPM 测试的获得阶段前腹膜内给药。
二甲双胍逆转了东莨菪碱引起的学习和记忆障碍。此外，二甲双胍提高了磷酸化 AMP 激活蛋白激酶和 cAMP 反应元件结合蛋白的水平。然而，二甲双胍预处理对抑制东莨菪碱引起的乙酰胆碱水平变化没有影响。此外，二甲双胍通过显著逆转东莨菪碱引起的海马丙二醛、总抗氧化状态和超氧化物歧化酶水平的变化发挥其抗氧化作用。
我们的结果表明，最常用的降糖药之一二甲双胍有可能预防痴呆的发生，并成为改善 AD 认知功能障碍的一种新的治疗药物。
