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题名: Metabolomics Approach Reveals Integrated Metabolic Network Associated with Serotonin Deficiency
作者: Weng, Rui1;  Shen, Sensen1;  Tian, Yonglu2;  Burton, Casey3, 4;  Xu, Xinyuan1;  Liu, Yi1;  Chang, Cuilan1;  Bai, Yu1;  Liu, Huwei1
刊名: SCIENTIFIC REPORTS
发表日期: 2015-07-08
DOI: 10.1038/srep11864
卷: 5
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Multidisciplinary Sciences
研究领域[WOS]: Science & Technology - Other Topics
英文摘要: Serotonin is an important neurotransmitter that broadly participates in various biological processes. While serotonin deficiency has been associated with multiple pathological conditions such as depression, schizophrenia, Alzheimer's disease and Parkinson's disease, the serotonin-dependent mechanisms remain poorly understood. This study therefore aimed to identify novel biomarkers and metabolic pathways perturbed by serotonin deficiency using metabolomics approach in order to gain new metabolic insights into the serotonin deficiency-related molecular mechanisms. Serotonin deficiency was achieved through pharmacological inhibition of tryptophan hydroxylase (Tph) using p-chlorophenylalanine (pCPA) or genetic knockout of the neuronal specific Tph2 isoform. This dual approach improved specificity for the serotonin deficiency-associated biomarkers while minimizing nonspecific effects of pCPA treatment or Tph2 knockout (Tph2-/-). Non-targeted metabolic profiling and a targeted pCPA dose-response study identified 21 biomarkers in the pCPA-treated mice while 17 metabolites in the Tph2-/- mice were found to be significantly altered compared with the control mice. These newly identified biomarkers were associated with amino acid, energy, purine, lipid and gut microflora metabolisms. Oxidative stress was also found to be significantly increased in the serotonin deficient mice. These new biomarkers and the overall metabolic pathways may provide new understanding for the serotonin deficiency-associated mechanisms under multiple pathological states.
关键词[WOS]: PARKINSONS-DISEASE ;  ALZHEIMERS-DISEASE ;  BRAIN-SEROTONIN ;  TRYPTOPHAN-METABOLISM ;  PSYCHIATRIC-DISORDERS ;  P-CHLOROPHENYLALANINE ;  TARGETED METABOLOMICS ;  DRUG DEVELOPMENT ;  ACID LEVELS ;  URIC-ACID
语种: 英语
WOS记录号: WOS:000357576800001
Citation statistics: 
内容类型: 期刊论文
URI标识: http://cas-ir.dicp.ac.cn/handle/321008/146383
Appears in Collections:中国科学院大连化学物理研究所_期刊论文

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作者单位: 1.Peking Univ, Beijing Natl Lab Mol Sci, Key Lab Bioorgan Chem & Mol Engn, Minist Educ,Inst Analyt Chem,Coll Chem & Mol Engn, Beijing 100871, Peoples R China
2.Peking Univ, Lab Anim Ctr, Beijing 100871, Peoples R China
3.Missouri Univ Sci & Technol, Dept Chem, Rolla, MO 65409 USA
4.Missouri Univ Sci & Technol, Ctr Biomed Sci & Engn, Rolla, MO 65409 USA

Recommended Citation:
Weng, Rui,Shen, Sensen,Tian, Yonglu,et al. Metabolomics Approach Reveals Integrated Metabolic Network Associated with Serotonin Deficiency[J]. SCIENTIFIC REPORTS,2015,5.
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