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Metformin improves depressive-like symptoms in mice via inhibition of peripheral and central NF-κB-NLRP3 inflammation activation.
Experimental Brain Research ( IF 1.7 ) Pub Date : 2020-09-01 , DOI: 10.1007/s00221-020-05911-x
Ren-Wei Du 1 , Wen-Guang Bu 1
Affiliation  

Emerging evidence indicates that NLRP3 inflammasome-induced inflammation plays a crucial role in the pathogenesis of depression. Thus, inhibition of NLRP3 inflammasome activation may offer a therapeutic benefit in the treatment of depression. Metformin has been shown to have potential anti-inflammatory activity, but the underlying mechanisms remain obscure. We used a chronic mild stress model of depression and cultured primary macrophage to investigate the effects of metformin on depression and its underlying mechanisms. We demonstrated that metformin alleviated depressive-like behaviors in the chronic mild stress-induced anhedonia model of depression. We further found that metformin significantly suppressed NLRP3 inflammasome activation, subsequent caspase-1 cleavage, and interleukin-1β secretion in both peripheral macrophages and central hippocampus. Our findings reveal that metformin confers an antidepressant effect partly through inhibition of peripheral and central NLRP3 inflammasome activation. In light of metformin favorable properties, it should be evaluated in the treatment of depression and related neurologic disorders characterized by NLRP3 inflammasome activation.



中文翻译:

二甲双胍通过抑制周围和中枢NF-κB-NLRP3炎症激活来改善小鼠的抑郁样症状。

新兴证据表明,NLRP3炎性体诱导的炎症在抑郁症的发病机理中起着至关重要的作用。因此,抑制NLRP3炎性体的活化可以在抑郁症的治疗中提供治疗益处。二甲双胍已被证明具有潜在的抗炎活性,但其潜在机制仍不清楚。我们使用抑郁症的慢性轻度应激模型和培养的初级巨噬细胞来研究二甲双胍对抑郁症的影响及其潜在机制。我们证明了二甲双胍减轻了慢性轻度应激诱发的抑郁症的快感缺乏症的抑郁样行为。我们还发现,二甲双胍显着抑制了NLRP3炎性体的激活,随后抑制了caspase-1的裂解,外周巨噬细胞和中央海马中白细胞介素和白细胞介素1β的分泌。我们的发现表明,二甲双胍部分通过抑制外周和中枢NLRP3炎性体激活而赋予抗抑郁作用。鉴于二甲双胍的良好特性,应在治疗以NLRP3炎症小体活化为特征的抑郁症和相关神经系统疾病中进行评估。

更新日期:2020-09-01
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