Effects of pharmacological treatment on metabolomic alterations in animal models of depression

作者全名："Pu, Juncai; Liu, Yiyun; Gui, Siwen; Tian, Lu; Yu, Yue; Wang, Dongfang; Zhong, Xiaogang; Chen, Weiyi; Chen, Xiaopeng; Chen, Yue; Chen, Xiang; Gong, Xue; Liu, Lanxiang; Li, Wenxia; Wang, Haiyang; Xie, Peng"

作者地址："[Pu, Juncai; Chen, Weiyi; Chen, Xiaopeng; Chen, Yue; Chen, Xiang; Gong, Xue; Liu, Lanxiang; Li, Wenxia; Wang, Haiyang; Xie, Peng] Chongqing Med Univ, Affiliated Hosp 1, Dept Neurol, Chongqing 400016, Peoples R China; [Pu, Juncai; Liu, Yiyun; Gui, Siwen; Tian, Lu; Wang, Dongfang; Zhong, Xiaogang; Chen, Weiyi; Chen, Xiaopeng; Chen, Yue; Chen, Xiang; Gong, Xue; Xie, Peng] Chongqing Med Univ, Affiliated Hosp 1, NHC Key Lab Diag & Treatment Brain Funct Dis, Chongqing 400016, Peoples R China; [Yu, Yue] Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55901 USA"

通信作者："Xie, P (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Neurol, Chongqing 400016, Peoples R China.; Xie, P (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, NHC Key Lab Diag & Treatment Brain Funct Dis, Chongqing 400016, Peoples R China."

来源：TRANSLATIONAL PSYCHIATRY

ESI学科分类：PSYCHIATRY/PSYCHOLOGY

WOS号：WOS:000788856700002

JCR分区：Q1

影响因子：6.8

年份：2022

卷号：12

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：　

摘要："Numerous studies have investigated metabolite alterations resulting from pharmacological treatment in depression models although few quantitative studies explored metabolites exhibiting constant alterations. This study aimed to identify consistently dysregulated metabolites across such studies using a knowledgebase-driven approach. This study was based on 157 studies that identified an assembly of 2757 differential metabolites in the brain, blood, urine, liver, and feces samples of depression models with pharmacological medication. The use of a vote-counting approach to identify consistently upregulated and downregulated metabolites showed that serotonin, dopamine, norepinephrine, gamma-aminobutyric acid, anandamide, tryptophan, hypoxanthine, and 3-methoxytyramine were upregulated in the brain, while quinolinic acid, glutamic acid, 5-hydroxyindoleacetic acid, myo-inositol, lactic acid, and the kynurenine/tryptophan ratio were downregulated. Circulating levels of trimethylamine N-oxide, isoleucine, leucine, tryptophan, creatine, serotonin, valine, betaine, and low-density lipoprotein were elevated. In contrast, levels of alpha-d-glucose, lactic acid, N-acetyl glycoprotein, glutamine, beta-d-glucose, corticosterone, alanine, phenylacetylglycine, glycine, high-density lipoprotein, arachidonic acid, myo-inositol, allantoin, and taurine were decreased. Moreover, 12 metabolites in urine and nine metabolites in the liver were dysregulated after treatment. Pharmacological treatment also increased fecal levels of butyric acid, acetic acid, propionic acid, and isovaleric acid. Collectively, metabolite disturbances induced by depression were reversed by pharmacological treatment. Pharmacological medication reversed the reduction of brain neurotransmitters caused by depression, modulated disturbance of the tryptophan-kynurenine pathway and inflammatory activation, and alleviated abnormalities of amino acid metabolism, energy metabolism, lipid metabolism, and gut microbiota-derived metabolites."

基金机构："National Key Research and Development Program of China [2017YFA0505700]; Non-profit Central Research Institute Fund of the Chinese Academy of Medical Sciences [2019PT320002]; Natural Science Foundation Project of China [81820108015, 82101596]; Young Elite Scientists Sponsorship Program by CAST [2021QNRC001]; China Postdoctoral Science Foundation [2021MD703926, 2021MD693926, 2020TQ0393, 2020M683634XB]"

基金资助正文："We thank Liwen Bianji (Edanz) (www.liwenbianji.cn/) for basic language editing of a draft of this manuscript. This work was supported by the National Key Research and Development Program of China (Grant no. 2017YFA0505700), the Non-profit Central Research Institute Fund of the Chinese Academy of Medical Sciences (Grant no. 2019PT320002), the Natural Science Foundation Project of China (Grant no. 81820108015 and 82101596), the Young Elite Scientists Sponsorship Program by CAST (Grant no. 2021QNRC001), and the China Postdoctoral Science Foundation (Grant no. 2021MD703926, 2021MD693926, 2020TQ0393, and 2020M683634XB)."