Proteomics reveals mitochondrial dysfunction and energy metabolism disturbance of intestine in a nonhuman primate model of depression

作者全名："Chen, Xiaopeng; Liu, Yiyun; Pu, Juncai; Gui, Siwen; Wang, Dongfang; Zhong, Xiaogang; Chen, Weiyi; Tao, Wei; Chen, Yue; Chen, Xiang; Xie, Peng"

作者地址："[Chen, Xiaopeng; Liu, Yiyun; Pu, Juncai; Gui, Siwen; Wang, Dongfang; Zhong, Xiaogang; Chen, Weiyi; Tao, Wei; Chen, Yue; Chen, Xiang; Xie, Peng] Chongqing Med Univ, NHC Key Lab Diag & Treatment Brain Funct Dis, Affiliated Hosp 1, Chongqing 400016, Peoples R China; [Chen, Xiaopeng; Liu, Yiyun; Pu, Juncai; Chen, Weiyi; Chen, Yue; Chen, Xiang; Xie, Peng] Chongqing Med Univ, Dept Neurol, Affiliated Hosp 1, Chongqing 400016, Peoples R China; [Xie, Peng] Chongqing Med Univ, Dept Neurol, Affiliated Hosp 1, 1 Youyi Rd, Chongqing 400016, Peoples R China"

通信作者："Xie, P (通讯作者)，Chongqing Med Univ, Dept Neurol, Affiliated Hosp 1, 1 Youyi Rd, Chongqing 400016, Peoples R China."

来源：JOURNAL OF AFFECTIVE DISORDERS

ESI学科分类：PSYCHIATRY/PSYCHOLOGY

WOS号：WOS:001031389200001

JCR分区：Q1

影响因子：6.6

年份：2023

卷号：333

期号：　

开始页：562

结束页：570

文献类型：Article

关键词：Depression; Nonhuman primates; Intestine; Proteomics; Mitochondria; Energy metabolism

摘要："Background: The gut-brain axis has been shown to play an important role in depression. However, few studies have examined proteomic changes in the intestine of the nonhuman primate model of depression. Methods: We investigated the intestinal proteome of macaques (Macaca fascicularis) with depression-like (DL) behaviors by data-independent acquisition techniques. We also performed integration analyses of proteomic changes, previous metabolomic and microbiotic data. Moreover, we confirmed the gene expressions of key proteins. Results: Sixty-five differentially expressed proteins (DEPs) were identified, of which fifty-four DEPs were downregulated and the others were altered conversely in DL macaques compared with the control group. Pathway analysis indicated that mitochondrial function and energy metabolism were representative functions of DEPs. The key DEPs were significantly associated with glycerophospholipid metabolism and imbalances of gut microbe. We confirmed that key molecules (NDUFB4, UQCR10, PISD) were significantly inhibited, which may disturb the energy transformation of the electron respiratory chain and the homeostasis of the mitochondrial membrane. Limitations: Further research is warranted to determine the effects of depression on other peripheral organs. Conclusions: These findings suggest the functional disorder of intestinal mitochondria in DL macaques. The disturbances of glycerophospholipid metabolism and gut microbiota may exacerbate disruptions of energy metabolism. Taking together, our study provides new clues to the relationship between depression and intestinal proteome."

基金机构："National Key Research and Devel- opment Program of China [2017YFA0505700]; Natural Science Foundation Project of China [81820108015, 82101596]; Young Elite Scientists Sponsorship Program by CAST [2021QNRC001]; Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences [2019PT320002]; Chongqing Science and Technology Commission [cstc2022ycjh-bgzxm0033]"

基金资助正文：This work was supported by the National Key Research and Devel- opment Program of China (Grant no. 2017YFA0505700) ; the Natural Science Foundation Project of China (Grant no. 81820108015 and 82101596) ; Young Elite Scientists Sponsorship Program by CAST (Grant no. 2021QNRC001) ; the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (2019PT320002) ; and the insti- tutional funds from the Chongqing Science and Technology Commission (Grant no. cstc2022ycjh-bgzxm0033) .