title: Metabolomics Approach Reveals Integrated Metabolic Network Associated with Serotonin Deficiency.
abstract: 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.
authors.affiliation: Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Institute of Analytical Chemistry, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Weng
authors.affiliation: Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Institute of Analytical Chemistry, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
authors.forename: Sensen
authors.initials: S
authors.lastname: Shen
authors.affiliation: Laboratory Animal Centre, Peking University, Beijing 100871, China.
authors.forename: Yonglu
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Department of Chemistry and Center for Biomedical Science &Engineering, Missouri University of Science and Technology, Rolla, MO 65409, USA.
authors.forename: Casey
authors.initials: C
authors.lastname: Burton
authors.affiliation: Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Institute of Analytical Chemistry, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
authors.forename: Xinyuan
authors.initials: X
authors.lastname: Xu
authors.affiliation: Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Institute of Analytical Chemistry, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Institute of Analytical Chemistry, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
authors.forename: Cuilan
authors.initials: C
authors.lastname: Chang
authors.affiliation: Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Institute of Analytical Chemistry, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Bai
authors.affiliation: Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Institute of Analytical Chemistry, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
authors.forename: Huwei
authors.initials: H
authors.lastname: Liu
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D015415:Biomarkers; D001921:Brain / Q000378:metabolism; D016000:Cluster Analysis; D010134:Fenclonine / Q000494:pharmacology; D005979:Glutathione Peroxidase / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D053858:Metabolic Networks and Pathways; D055442:Metabolome; D055432:Metabolomics / Q000379:methods; D051379:Mice; D018345:Mice, Knockout; D017382:Reactive Oxygen Species / Q000378:metabolism; D012701:Serotonin / Q000172:deficiency*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000378:metabolism; D014365:Tryptophan Hydroxylase / Q000172:deficiency / Q000235:genetics
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D017382:Reactive Oxygen Species; D012702:Serotonin Antagonists; D012701:Serotonin; D008315:Malondialdehyde; D005979:Glutathione Peroxidase; C487802:Tph2 protein, mouse; D014365:Tryptophan Hydroxylase; D013482:Superoxide Dismutase; D010134:Fenclonine