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Depression-like behaviors are accompanied by disrupted mitochondrial energy metabolism in chronic corticosterone-induced mice.

抑郁样行为伴随着慢性皮质酮诱导小鼠线粒体能量代谢紊乱。

  • 影响因子:3.73
  • DOI:10.1016/j.jsbmb.2020.105607
  • 作者列表:"Xie X","Shen Q","Yu C","Xiao Q","Zhou J","Xiong Z","Li Z","Fu Z
  • 发表时间:2020-02-08
Abstract

:Stress exerts its negative effects by interference with mitochondrial energy production in rodents, and is able to impair mitochondrial bioenergetics. However, the underlying mechanism that stress hormone impacts depression-like behaviors and mitochondrial energy metabolism is still not well understood. Here, we investigated the changes of depression-like behaviors and mitochondrial energy metabolism induced by chronic corticosterone (CORT). The results showed that after treatment with CORT for 6 weeks, mice displayed depression-like behaviors, which were identified by tail suspension test, forced swimming test and open field test. Then, the livers were isolated and tested by RNA sequencing and metabolome analysis. RNA sequencing showed 354 up-regulated genes and 284 down-regulated genes, and metabolome analysis revealed 280 metabolites with increased abundances and 193 metabolites with reduced abundances in the liver of mice after CORT, which were closely associated with lipid metabolism and oxidative phosphorylation in mitochondria. Based on these findings, the changes of mitochondrial energy metabolism were investigated, and we revealed that CORT condition inhibited glycolysis and fatty acid degradation pathway, and activated synthesis of triacylglycerol, leading to the reduced levels of acetyl-CoA and attenuated TCA cycle. Also, the pathways of NAD+ synthesis were inhibited, resulting in the reduced activity of sirtuin 3 (SIRT3). Thus, all of these observations disrupted the function of mitochondria, and led to the decrease of ATP production. Our findings uncover a novel mechanism of stress on depression-like behaviors and mitochondrial energy metabolism in rodents.

摘要

: 应激通过干扰啮齿类动物线粒体能量产生发挥其负面作用,并能够损害线粒体生物能量学。然而,应激激素影响抑郁样行为和线粒体能量代谢的潜在机制仍不清楚。在此,我们研究了慢性皮质酮 (CORT) 诱导的抑郁样行为和线粒体能量代谢的变化。结果表明,CORT 治疗 6 周后,小鼠表现出抑郁样行为,通过悬尾试验、强迫游泳试验和旷场试验进行鉴定。然后,分离肝脏,通过 RNA 测序和代谢组分析进行检测。RNA 测序显示 354 个上调基因和 284 个下调基因,代谢组分析发现 CORT 后小鼠肝脏中 280 个丰度增加的代谢物和 193 个丰度减少的代谢物, 与线粒体脂质代谢和氧化磷酸化密切相关。基于这些发现,研究了线粒体能量代谢的变化,我们发现 CORT 条件抑制糖酵解和脂肪酸降解途径,并激活三酰甘油的合成, 导致乙酰辅酶a 水平降低,TCA 循环减弱。同样,NAD + 合成的途径被抑制,导致 sirtuin 3 (SIRT3) 的活性降低。因此,所有这些观察破坏了线粒体的功能,并导致 ATP 产生的减少。我们的研究结果揭示了应激对啮齿类动物抑郁样行为和线粒体能量代谢的新机制。

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翻译标题与摘要 下载文献
影响因子:2.76
发表时间:2020-01-30
DOI:10.1152/japplphysiol.00631.2019
作者列表:["Bonomi AG","Ten Hoor GA","De Morree HM","Plasqui G","Sartor F"]

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翻译标题与摘要 下载文献
影响因子:3.76
发表时间:2020-01-31
DOI:10.1152/ajpgi.00386.2018
作者列表:["Farr S","Stankovic B","Hoffman S","Masoudpoor H","Baker C","Taher J","Dean A","Anakk S","Adeli K"]

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