Metabolite signature associated with stress susceptibility in socially defeated mice

Prabhu, Vishwanath Vasudev; Nguyen, Thong Ba; Cui, Yin; Oh, Youngmin; Piao, Yan Hong; Baek, Hyeon‐Man; Kim, Joo-Yeon; Shin, Kyung‐Jae; Kim, Jihyun; Lee, Keon-Hak; Chung, Young‐Chul

doi:10.1016/j.brainres.2018.12.020

Cited by 14 publications

(12 citation statements)

References 65 publications

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“…Because of the important physiological role of metabolites, these metabolomics techniques have been widely used to identify biochemical disturbances in diseases [9]. To date, hundreds of metabolomics studies have been conducted to investigate the metabolite alterations in animal models of depression, which expanded the knowledge of the physiopathology of depression [10][11][12]. Moreover, supplementation with certain metabolites could exert antidepressant effects, suggesting that metabolomics techniques are potential strategies for screening and developing new antidepressants [13][14][15].…”

Section: Introductionmentioning

confidence: 99%

Metabolomic changes in animal models of depression: a systematic analysis

Liu

Gui

et al. 2021

Mol Psychiatry

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Extensive research has been carried out on the metabolomic changes in animal models of depression; however, there is no general agreement about which metabolites exhibit constant changes. Therefore, the aim of this study was to identify consistently altered metabolites in large-scale metabolomics studies of depression models. We performed vote counting analyses to identify consistently upregulated or downregulated metabolites in the brain, blood, and urine of animal models of depression based on 3743 differential metabolites from 241 animal metabolomics studies. We found that serotonin, dopamine, gamma-aminobutyric acid, norepinephrine, N-acetyl-L-aspartic acid, anandamide, and tryptophan were downregulated in the brain, while kynurenine, myo-inositol, hydroxykynurenine, and the kynurenine to tryptophan ratio were upregulated. Regarding blood metabolites, tryptophan, leucine, tyrosine, valine, trimethylamine N-oxide, proline, oleamide, pyruvic acid, and serotonin were downregulated, while N-acetyl glycoprotein, corticosterone, and glutamine were upregulated. Moreover, citric acid, oxoglutaric acid, proline, tryptophan, creatine, betaine, L-dopa, palmitic acid, and pimelic acid were downregulated, and hippuric acid was upregulated in urine. We also identified consistently altered metabolites in the hippocampus, prefrontal cortex, serum, and plasma. These findings suggested that metabolomic changes in depression models are characterized by decreased neurotransmitter and increased kynurenine metabolite levels in the brain, decreased amino acid and increased corticosterone levels in blood, and imbalanced energy metabolism and microbial metabolites in urine. This study contributes to existing knowledge of metabolomic changes in depression and revealed that the reproducibility of candidate metabolites was inadequate in previous studies.

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Section: Introductionmentioning

confidence: 99%

Metabolomic changes in animal models of depression: a systematic analysis

Liu

Gui

et al. 2021

Mol Psychiatry

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“…Additionally, in order to improve spectral resolution [ 18 ], the HR-MAS technique is to be applied to the swollen sample in a suitable NMR solvent that provides some molecular motions [ 19 , 22 ]. In addition to the liquid state, HR-MAS NMR has been used in metabolic analyses in human, plant, and food stuff quality managements, genotype, phenotype, and organism cataloging, with interindividual comparisons, environmental toxicity, and pollution [ 24 , 25 , 26 , 27 , 28 , 29 , 30 ]. Moreover, crowded spectral overlaps and chemical structure elucidations can be facilitated by mapping all homo- and heteronuclear correlations through multidimensional (nD) NMR approaches [ 31 ].…”

Section: Introductionmentioning

confidence: 99%

High-Resolution Magic Angle Spinning (HR-MAS) NMR-Based Fingerprints Determination in the Medicinal Plant Berberis laurina

et al. 2020

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Berberis laurina (Berberidaceae) is a well-known medicinal plant used in traditional medicine since ancient times; however, it is scarcely studied to a large-scale fingerprint. This work presents a broad-range fingerprints determination through high-resolution magical angle spinning (HR-MAS) nuclear magnetic resonance (NMR) spectroscopy, a well-established flexible analytical method and one of most powerful “omics” platforms. It had been intended to describe a large range of chemical compositions in all plant parts. Beyond that, HR-MAS NMR allowed the direct investigation of botanical material (leaves, stems, and roots) in their natural, unaltered states, preventing molecular changes. The study revealed 17 metabolites, including caffeic acid, and berberine, a remarkable alkaloid from the genus Berberis L. The metabolic pattern changes of the leaves in the course of time were found to be seasonally dependent, probably due to the variability of seasonal and environmental trends. This metabolites overview is of great importance in understanding plant (bio)chemistry and mediating plant survival and is influenceable by interacting environmental means. Moreover, the study will be helpful in medicinal purposes, health sciences, crop evaluations, and genetic and biotechnological research.

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“…Several previous studies indicate that both stress (Dulka et al, 2017;Prabhu et al, 2019) and fluoxetine or ketamine treatment can significantly alter metabolic profiles (Weckmann, Labermaier, Asara, Muller, & Turck, 2014;Zhao et al, 2015Zhao et al, , 2019. Therefore, we used multi-platform targeted metabolomics from the frontal part of the cortex to study the amino acids (AA) and their metabolites as well as several acylcarnitines (AC).…”

Section: Antidepressant Treatment and Decreased Mitochondrial Function Resulted In Metabolic Rewiringmentioning

confidence: 99%

Chronic fluoxetine or ketamine treatment differentially affects brain energy homeostasis which is not exacerbated in mice with trait suboptimal mitochondrial function

Emmerzaal

Jacobs

Geenen

et al. 2020

Eur J of Neuroscience

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Antidepressants have been shown to influence mitochondrial function directly, and suboptimal mitochondrial function (SMF) has been implicated in complex psychiatric disorders. In the current study, we used a mouse model for trait SMF to test the hypothesis that chronic fluoxetine treatment in mice subjected to chronic stress would negatively impact brain bioenergetics, a response that would be more pronounced in mice with trait SMF. In contrast, we hypothesized that chronic ketamine treatment would positively impact mitochondrial function in both WT and mice with SMF. We used an animal model for trait SMF, the Ndufs4 GT/GT mice, which exhibit 25% lower mitochondrial complex I activity. In addition to antidepressant treatment, mice were subjected to chronic unpredictable stress (CUS). This paradigm is widely used to model complex behaviours expressed in various psychiatric disorders. We assayed several physiological indices as proxies for the impact of chronic stress and antidepressant treatment. Furthermore, we measured brain mitochondrial complex activities using clinically validated assays as well as established metabolic signatures using targeted metabolomics. As hypothesized, we found evidence that chronic fluoxetine treatment negatively impacted brain bioenergetics. This phenotype was, however, not further exacerbated in mice with trait SMF. Ketamine did not have a significant influence on brain mitochondrial function in either genotype. Here we report that trait SMF could be a moderator for an individual's response to antidepressant treatment. Based on these results, we propose that in individuals with SMF and comorbid psychopathology, fluoxetine should be avoided, whereas ketamine could be a safer choice of treatment.

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Metabolite signature associated with stress susceptibility in socially defeated mice

Cited by 14 publications

References 65 publications

Metabolomic changes in animal models of depression: a systematic analysis

Metabolomic changes in animal models of depression: a systematic analysis

High-Resolution Magic Angle Spinning (HR-MAS) NMR-Based Fingerprints Determination in the Medicinal Plant Berberis laurina

Chronic fluoxetine or ketamine treatment differentially affects brain energy homeostasis which is not exacerbated in mice with trait suboptimal mitochondrial function

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