Depression-like behaviors are accompanied by disrupted mitochondrial energy metabolism in chronic corticosterone-induced mice. Issue 200 (June 2020)

• Record Type: Journal Article
• Authors: Xie, Xiaoxian; Shen, Qichen; Yu, Chunan; Xiao, Qingfeng; Zhou, Jiafeng; Xiong, Ze; Li, Zezhi; Fu, Zhengwei
• Is Part Of: Journal of steroid biochemistry and molecular biology. Issue 200(2020)
• Publication Date: 2020-06
• Subjects: Depression -- Mitochondrial function -- Energy metabolism -- NAD+ -- SIRT3; Steroid hormones -- Periodicals; Biochemistry -- Periodicals; Hormones -- Periodicals; Molecular Biology -- Periodicals; Hormones stéroïdes -- Périodiques; Steroid hormones; Periodicals; 572.579
• DOI: 10.1016/j.jsbmb.2020.105607
• Languages: English
• ISSNs: 0960-0760

Abstract

Highlights: CORT alters mitochondria energy-related transcriptome and metabolomics profiles. CORT injection disrupts mitochondrial energy metabolism in depressive mice. ATP production is inhibited via NAD + synthesis and SIRT3 signaling pathway. 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.