Metformin Ameliorates Lipopolysaccharide-Induced Depressive-Like Behaviors and Abnormal Glutamatergic Transmission.
Metformin Ameliorates Lipopolysaccharide-Induced Depressive-Like Behaviors and Abnormal Glutamatergic Transmission.
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二甲双胍可改善脂多糖引起的抑郁样行为和异常谷氨酸传递。
DOI：
10.3390/biology9110359
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发表时间：
2020-10-26
期刊：
影响因子：
4.2
通讯作者：
Fei EK
中科院分区：
文献类型：
--
作者：
Chen J;Zhou T;Guo AM;Chen WB;Lin D;Liu ZY;Fei EK
二甲双胍是一种很有前途的糖尿病药物，据报道，它对抑郁症患者或抑郁症与其他疾病共病的患者具有抗抑郁作用。然而，目前还不清楚二甲双胍如何改善抑郁样行为。为此，我们向小鼠注射细菌内毒素（脂多糖），以诱导抑郁样行为，例如在强迫游泳试验和悬尾试验中增加不动性。在该抑郁小鼠模型中，二甲双胍给药改善了抑郁样行为。谷氨酸是大脑中神经元之间通信的主要兴奋信号。多巴胺能神经传递功能障碍与抑郁症的发病机制有关。在我们的抑郁症小鼠模型中，谷氨酸能传递升高。二甲双胍给药也恢复了模型中的多巴胺能传递缺陷。综上所述，我们的结果表明二甲双胍具有抗抑郁作用，可以纠正脂多糖诱导的抑郁小鼠模型中的异常多巴胺能传递。这些发现为二甲双胍对抗抑郁症的潜在机制提供了新的见解。二甲双胍是治疗2型糖尿病（T2DM）的一线药物，已发现可减轻抑郁症和其他疾病共病患者的抑郁症状。然而，目前还不清楚二甲双胍如何改善抑郁样行为。在这里，我们使用脂多糖（LPS）诱导小鼠抑郁样行为，发现LPS处理的小鼠在强迫游泳试验（FST）和悬尾试验（TST）中表现出增加的不动性，以及增加的多巴胺能传递。此外，二甲双胍给药LPS处理的小鼠改善抑郁样行为和升高的多巴胺能传递。我们的研究结果表明，二甲双胍具有抗抑郁作用，可以纠正异常的多巴胺能传递，从而深入了解二甲双胍抗抑郁的潜在机制。
Metformin is a promising drug for diabetes and has been reported to have antidepressant effects in depression patients or patients with comorbid depression and other diseases. However, it is largely unclear how metformin ameliorates depressive-like behaviors. To this end, we injected mice with a bacterial endotoxin (lipopolysaccharide) to induce depressive-like behaviors such as increased immobility in the forced swimming test and tail suspension test. In this depression mouse model, metformin administration ameliorated depressive-like behaviors. Glutamate is a major excitatory signal for the communications between neurons in the brain. Dysfunction of glutamatergic neurotransmission is implicated in the pathogenesis of depression. Glutamatergic transmission was elevated in our depression mouse model. Metformin administration also recovered the glutamatergic transmission deficit in the model. Taken together, our results suggest metformin had antidepressant effects and can correct abnormal glutamatergic transmission in the lipopolysaccharide-induced depression mouse model. These findings provide new insights into the underlying mechanism by which metformin acts against depression. Metformin, a first-line drug for type 2 diabetes mellitus (T2DM), has been found to reduce depressive symptoms in patients with comorbid depression and other diseases. However, it is largely unclear how metformin ameliorates depressive-like behaviors. Here, we used lipopolysaccharide (LPS) to induce depressive-like behaviors in mice and found that LPS-treated mice exhibited increased immobility in the forced swimming test (FST) and tail suspension test (TST), as well as increased glutamatergic transmission. Furthermore, metformin administration in the LPS-treated mice ameliorated depressive-like behaviors and elevated glutamatergic transmission. Our results suggest that metformin has antidepressant effects and can correct abnormal glutamatergic transmission, providing an insight into the underlying mechanism by which metformin acts against depression.
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