Antidiabetic Drug Metformin Ameliorates Depressive-Like Behavior in Mice with Chronic Restraint Stress via Activation of AMP-Activated Protein Kinase
Antidiabetic Drug Metformin Ameliorates Depressive-Like Behavior in Mice with Chronic Restraint Stress via Activation of AMP-Activated Protein Kinase
复制标题
抗糖尿病药物二甲双胍通过激活 AMP 激活的蛋白激酶改善慢性束缚应激小鼠的抑郁样行为
DOI：
10.14336/ad.2019.0403
复制
发表时间：
2020-02-01
影响因子：
7.4
通讯作者：
Lu, Wen
中科院分区：
文献类型：
--
作者：
Ali, Heng;Fang, Weiqing;Lu, Wen
抑郁症是现代社会最常见的神经精神疾病之一。然而，传统药物，如单胺能药物，具有需要数周至数月的滞后反应的缺陷。此外，这些药物在抑郁症患者中的疗效有限，耐药率高。因此，迫切需要开发用于治疗抑郁症的新型药物或方法。在这里，使用生物化学，药理学，遗传学和行为学方法，我们证明二甲双胍在未经处理的小鼠以及慢性束缚应激模型的应激小鼠中具有快速作用的抗抑郁样作用。此外，化合物C抑制AMPK活性或敲低海马AMPKα阻断了二甲双胍诱导的抗抑郁样作用。我们的研究结果表明，二甲双胍可能是一种可行的治疗药物，通过激活AMPK治疗应激诱导的抑郁症。
Depression is one of the most prevalent neuropsychiatric disorders in modern society. However, traditional drugs, such as monoaminergic agents, have defect showing lag response requiring several weeks to months. Additionally, these drugs have limited efficacy and high resistance rates in patients with depression. Thus, there is an urgent need to develop novel drugs or approaches for the treatment of depression. Here, using biochemical, pharmacological, genetic and behavioral methods, we demonstrate that metformin imparts a fast-acting antidepressant-like effect in naïve mice as well as stressed mice subjected to chronic restraint stress model. Moreover, inhibition of AMP-activated protein kinase (AMPK) activity by compound C or knock down of hippocampal AMPKα occluded the antidepressant-like effect induced by metformin. Our results suggest that metformin may be a viable therapeutic drug for the treatment of stress-induced depression via activation of AMPK.