Metabolomic identification of biochemical changes induced by fluoxetine and imipramine in a chronic mild stress mouse model of depression

Scientific Reports
Jing ZhaoJeongmi Lee

Abstract

Metabolomics was applied to a C57BL/6N mouse model of chronic unpredictable mild stress (CMS). Such mice were treated with two antidepressants from different categories: fluoxetine and imipramine. Metabolic profiling of the hippocampus was performed using gas chromatography-mass spectrometry analysis on samples prepared under optimized conditions, followed by principal component analysis, partial least squares-discriminant analysis, and pair-wise orthogonal projections to latent structures discriminant analyses. Body weight measurement and behavior tests including an open field test and the forced swimming test were completed with the mice as a measure of the phenotypes of depression and antidepressive effects. As a result, 23 metabolites that had been differentially expressed among the control, CMS, and antidepressant-treated groups demonstrated that amino acid metabolism, energy metabolism, adenosine receptors, and neurotransmitters are commonly perturbed by drug treatment. Potential predictive markers for treatment effect were identified: myo-inositol for fluoxetine and lysine and oleic acid for imipramine. Collectively, the current study provides insights into the molecular mechanisms of the antidepressant effects of two wi...Continue Reading

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Citations

Jun 4, 2015·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Jinping JiaLiwei Zhang
Jun 23, 2015·Frontiers in Pharmacology·Kazuki SakataNorio Ishida
Sep 10, 2016·Scientific Reports·Xixia ChuWeidong Li
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Sep 16, 2016·Acupuncture in Medicine : Journal of the British Medical Acupuncture Society·Yuxue ZhaoBing Zhu
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Jul 6, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Xinyi GuMingmei Zhou
Jun 18, 2017·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Zheng MouJun-Tian Zhang

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Methods Mentioned

BETA
metabolomics
PCA

Software Mentioned

OPLS
Enhanced ChemStation
XCMS
SIMCA
GraphPad
Prism
NeuroVision
DA

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