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

Zhao J, Jung YH, Jang CG, Chun KH, Kwon SW, Lee J - Sci Rep (2015)

Bottom Line: 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 widely used medications.

View Article: PubMed Central - PubMed

Affiliation: School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.

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 widely used medications.

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PCA score plot derived from the GC-MS analysis of hippocampi from control, Cms, Flu, and Imi groups.(black squares, control; red circles, Cms; blue diamonds, Flu; green triangles, Imi).
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f4: PCA score plot derived from the GC-MS analysis of hippocampi from control, Cms, Flu, and Imi groups.(black squares, control; red circles, Cms; blue diamonds, Flu; green triangles, Imi).

Mentions: A PCA was used to visualize general clustering, trend, or outliers among the observations. Score plot and model analysis including Hotelling's T2 plot revealed no outliers. As seen in Supplementary Fig. S3, quality control samples were tightly clustered, which suggests that the quality of data was acceptable36. In the PCA score plot, the two drug-treated groups were separated from the Con and Cms groups, but no discernible clustering was observed between the Con and Cms groups or between the Flu and Imi groups (Fig. 4).


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

Zhao J, Jung YH, Jang CG, Chun KH, Kwon SW, Lee J - Sci Rep (2015)

PCA score plot derived from the GC-MS analysis of hippocampi from control, Cms, Flu, and Imi groups.(black squares, control; red circles, Cms; blue diamonds, Flu; green triangles, Imi).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4352870&req=5

f4: PCA score plot derived from the GC-MS analysis of hippocampi from control, Cms, Flu, and Imi groups.(black squares, control; red circles, Cms; blue diamonds, Flu; green triangles, Imi).
Mentions: A PCA was used to visualize general clustering, trend, or outliers among the observations. Score plot and model analysis including Hotelling's T2 plot revealed no outliers. As seen in Supplementary Fig. S3, quality control samples were tightly clustered, which suggests that the quality of data was acceptable36. In the PCA score plot, the two drug-treated groups were separated from the Con and Cms groups, but no discernible clustering was observed between the Con and Cms groups or between the Flu and Imi groups (Fig. 4).

Bottom Line: 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 widely used medications.

View Article: PubMed Central - PubMed

Affiliation: School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.

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 widely used medications.

Show MeSH
Related in: MedlinePlus