title: Biochemical effects of venlafaxine on astrocytes as revealed by1H NMR-based metabolic profiling.
abstract: As a serotonin-norepinephrine reuptake inhibitor [SNRI], venlafaxine is one of the most commonly prescribed clinical antidepressants, with a broad range of antidepressant effects. Accumulating evidence shows that venlafaxine may target astrocytes to exert its antidepressant activity, although the underlying pharmacological mechanisms remained largely unknown. Here, we used a1H nuclear magnetic resonance (NMR)-based metabonomics method coupled with multivariate statistical analysis to characterize the metabolic profiling of astrocytes treated with venlafaxine to explore the potential mechanism of its antidepressant effect. In total, 31 differential metabolites involved in energy, amino acid and lipid metabolism were identified. Ingenuity pathway analysis was used to identify the predicted pathways and biological functions with venlafaxine and fluoxetine. The most significantly altered network was "amino acid metabolism, cellular growth and proliferation", with a score above 20. Certain metabolites (lysine, tyrosine, glutamate, methionine, ethanolamine, fructose-6-phosphate, and phosphorylethanolamine) are involved in and play a central role in this network. Collectively, the biological effects of venlafaxine on astrocytes provide us with the further understanding of the mechanisms by which venlafaxine treats major depressive disorder.
authors.affiliation: Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing, 402460, China and Chongqing Key Laboratory of Neurobiology, Chongqing, 40016, China and Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, 40016, China and Key Laboratory of Laboratory Medical Diagnostics of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing, 40016, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing, 402460, China and Chongqing Key Laboratory of Neurobiology, Chongqing, 40016, China and Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, 40016, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Fang
authors.affiliation: Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing, 402460, China and Chongqing Key Laboratory of Neurobiology, Chongqing, 40016, China and Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, 40016, China and Key Laboratory of Laboratory Medical Diagnostics of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing, 40016, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Lian
authors.affiliation: Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing, 402460, China and Chongqing Key Laboratory of Neurobiology, Chongqing, 40016, China and Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, 40016, China and Key Laboratory of Laboratory Medical Diagnostics of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing, 40016, China.
authors.forename: Jin-Jun
authors.initials: JJ
authors.lastname: Xia
authors.affiliation: Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing, 402460, China and Chongqing Key Laboratory of Neurobiology, Chongqing, 40016, China and Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, 40016, China.
authors.forename: Chan-Juan
authors.initials: CJ
authors.lastname: Zhou
authors.affiliation: Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing, 402460, China and Chongqing Key Laboratory of Neurobiology, Chongqing, 40016, China and Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, 40016, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing, 402460, China and Chongqing Key Laboratory of Neurobiology, Chongqing, 40016, China and Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, 40016, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Mao
authors.affiliation: Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing, 402460, China and Chongqing Key Laboratory of Neurobiology, Chongqing, 40016, China and Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, 40016, China.
authors.forename: Xin-Fa
authors.initials: XF
authors.lastname: Wang
authors.affiliation: Chongqing Key Laboratory of Neurobiology, Chongqing, 40016, China and Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, 40016, China and Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 40016, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Gong
authors.affiliation: Chongqing Key Laboratory of Neurobiology, Chongqing, 40016, China and Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, 40016, China and Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 40016, China and Department of Neurology, The Inner Mongolia Autonomous Region People's Hospital, Hohhot, Inner Mongolia 010017, China.
authors.forename: Zi-Hong
authors.initials: ZH
authors.lastname: Liang
authors.affiliation: Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing, 402460, China and Chongqing Key Laboratory of Neurobiology, Chongqing, 40016, China and Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, 40016, China and Key Laboratory of Laboratory Medical Diagnostics of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing, 40016, China.
authors.forename: Shun-Jie
authors.initials: SJ
authors.lastname: Bai
authors.affiliation: Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing, 402460, China and Chongqing Key Laboratory of Neurobiology, Chongqing, 40016, China and Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, 40016, China and Key Laboratory of Laboratory Medical Diagnostics of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing, 40016, China.
authors.forename: Li
authors.initials: L
authors.lastname: Liao
authors.affiliation: Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing, 402460, China and Chongqing Key Laboratory of Neurobiology, Chongqing, 40016, China and Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, 40016, China and Key Laboratory of Laboratory Medical Diagnostics of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing, 40016, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing, 402460, China and Chongqing Key Laboratory of Neurobiology, Chongqing, 40016, China and Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, 40016, China and Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 40016, China.
authors.forename: Peng
authors.identifier: http://orcid.org/0000-0002-5338-9916
authors.initials: P
authors.lastname: Xie
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D055442:Metabolome; D055432:Metabolomics / Q000379:methods; D066244:Proton Magnetic Resonance Spectroscopy / Q000379:methods; D051381:Rats; D000069470:Venlafaxine Hydrochloride / Q000494:pharmacology*
chemical_list: D000069470:Venlafaxine Hydrochloride