A unique insight for energy metabolism disorders in depression based on chronic unpredictable mild stress rats using stable isotope-resolved metabolomics

Linghu, Ting; Gao, Yao; Li, Aiping; Shi, Bo; Tian, Jun-Sheng; Qin, Xuemei

doi:10.1016/j.jpba.2020.113588

Cited by 20 publications

(17 citation statements)

References 28 publications

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“…However, Ting et al (2020) proposed that AST may be a new target for depression [25], which was only confirmed in the samples of frontline anti-epidemic medical workers, in which depression significantly positively predicted the abnormality of biochemical indicator AST. This indicates that, in the case of major public health emergencies, it is more important to provide mental health assistance to frontline anti-epidemic medical personnel, because its impact on such personnel is not only reflected in changes appetite and sleep disorder, but is also reflected in their physical health indicators.…”

Section: Path Analysis and Mediating Effect Analysis Of Depressionmentioning

confidence: 99%

“…Moreover, studies have shown that abnormal AST represents the risk of fatty liver disease [23]. Ahmadi et al (2019) pointed out that after controlling for the influence of confounding factors, stress was significantly positively correlated with the biochemical factor AST [24], and the biochemical indicator AST may be a new target for depression [25]. Therefore, based on the stress background of the COVID-19 pandemic, this study investigates the mechanism of action between Type A personality, depression and biochemical indicator AST.…”

Section: Introductionmentioning

confidence: 99%

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The Pathways from Type A Personality to Physical and Mental Health Amid COVID-19: A Multiple-Group Path Model of Frontline Anti-Epidemic Medical Staff and Ordinary People

Wang

Tian

et al. 2021

IJERPH

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During the COVID-19 pandemic, a survey was conducted using the questionnaire method among participants consisting of both ordinary people (n = 325) and frontline anti-epidemic medical staff (n = 310), and physiological data was obtained on the basis of physical examination. This study aimed to scrutinize the influence of Type A personality on the biochemical indicators of aspartate aminotransferase (AST) and the behavioral indicators of appetite and sleep disorder, and to analyze the mediating effect of depression. Meanwhile, multiple-group path analysis was used to evaluate path differences between the models of two samples. The results of the mediation analysis for both samples demonstrated that depression significantly mediated the relationship between Type A personality and appetite and sleep disorder. The results of multiple-group path analysis showed that the relationship between Type A personality and appetite and sleep disorder seems to be significantly stronger in ordinary people, whereas the relationship between depression and appetite and sleep disorder, as well as with the path towards AST, seems to be significantly stronger in frontline anti-epidemic medical staff. This paper provides ideas for the selection and distribution of medical personnel based on personality characteristics in major public health emergencies, and physical and mental health status should be taken into account to provide relative health assistance.

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Section: Path Analysis and Mediating Effect Analysis Of Depressionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Pathways from Type A Personality to Physical and Mental Health Amid COVID-19: A Multiple-Group Path Model of Frontline Anti-Epidemic Medical Staff and Ordinary People

Wang

Tian

et al. 2021

IJERPH

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“…Abnormalities in metabolic pathways such as pyruvate metabolism, TCA cycle, and glycolysis/gluconeogenesis are mainly related to the disorder of energy metabolism. Many animal experiments have demonstrated that the pathophysiology of depression is closely related to a dysfunction of energy metabolism 34 , 35 . Glucose is the main energy-providing molecule in the body.…”

Section: Discussionmentioning

confidence: 99%

Serum metabolomic responses to aerobic exercise in rats under chronic unpredictable mild stress

Liu

Han

Zhou

et al. 2022

Sci Rep

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This study analyzed the effects of aerobic exercise on endogenous serum metabolites in response to chronic unpredictable mild stress (CUMS) using a rat model, aiming to identify the metabolic regulatory pathways involved in the antidepressant effect resulted from a 28-day treadmill aerobic exercise intervention. The animals were randomly divided into four groups (n = 8): normal control, normal with aerobic exercise, CUMS control, and CUMS with aerobic exercise. Body weight, sucrose preference and open field tests were performed weekly during the intervention period for changes in depressant symptoms. Serum metabolic profiles obtained by using the LC–MS/MS metabolomics were analyzed to explore the regulatory mechanism for the effect of the aerobic exercise on depression. Behavior tests showed that the aerobic exercise resulted in a significant improvement in depression-like behavior in the CUMS rats. A total of 21 differential metabolites were identified as being associated with depression in serum metabolic profile, of which the aerobic exercise significantly modulated 15, mainly related to amino acid metabolism and energy metabolism. Collectively, this is the first study that LC–MS/MS techniques were used to reveal the modulatory effects of aerobic exercise on the serum metabolic profile of depressed rats and the findings further enriched our understanding of potential mechanisms of aerobic exercise interventions on depression.

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“…In our previous study, 27 we have established a comprehensive method for stable isotope-resolved metabolomics, including the determination of introduction time and dose, the selection of chromatographic columns, the optimization of liquid chromatography mass spectrometry (LC−MS) parameters, and the extraction of isotopic information. Here, we applied this technique to decipher the abnormal brain glucose catabolism in CUMS rats and elaborate the pathogenesis of depression.…”

Section: ■ Introductionmentioning

confidence: 99%

“…The introduction of the stable isotope tracer (8.0 mg/kg•min) was conducted through tail vein injection for 6 h at 8.33 μL/min. Specific operations were performed according to the protocol described previously, 27 including the confirmation of the optimal time and the optimal dose of the stable isotope tracer.…”

Section: Stable Isotope Tracer Solution Preparation and Introductionmentioning

confidence: 99%

Stable Isotope-Resolved Metabolomics Reveals the Abnormal Brain Glucose Catabolism in Depression Based on Chronic Unpredictable Mild Stress Rats

et al. 2021

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The severe harm of depression to human life has attracted great attention to neurologists, but its pathogenesis is extremely complicated and has not yet been fully elaborated. Here, we provided a new strategy for revealing the specific pathways of abnormal brain glucose catabolism in depression, based on the supply of energy substrates and the evaluation of the mitochondrial structure and function. By using stable isotope-resolved metabolomics, we discovered that the tricarboxylic acid cycle (TCA cycle) is blocked and gluconeogenesis is abnormally activated in chronic unpredictable mild stress (CUMS) rats. In addition, our results showed an interesting phenomenon that the brain attempted to activate all possible metabolic enzymes in energy-producing pathways, but CUMS rats still exhibited a low TCA cycle activity due to impaired mitochondria. Depression caused the mitochondrial structure and function to be impaired and then led to abnormal brain glucose catabolism. The combination of the stable isotope-resolved metabolomics and mitochondrial structure and function analysis can accurately clarify the mechanism of depression. The mitochondrial pyruvate carrier and acetyl-CoA may be the key targets for depression treatment. The strategy provides a unique insight for exploring the mechanism of depression, the discovery of new targets, and the development of ideal novel antidepressants. Data are available via ProteomeXchange with identifier PXD025548.

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A unique insight for energy metabolism disorders in depression based on chronic unpredictable mild stress rats using stable isotope-resolved metabolomics

Cited by 20 publications

References 28 publications

The Pathways from Type A Personality to Physical and Mental Health Amid COVID-19: A Multiple-Group Path Model of Frontline Anti-Epidemic Medical Staff and Ordinary People

The Pathways from Type A Personality to Physical and Mental Health Amid COVID-19: A Multiple-Group Path Model of Frontline Anti-Epidemic Medical Staff and Ordinary People

Serum metabolomic responses to aerobic exercise in rats under chronic unpredictable mild stress

Stable Isotope-Resolved Metabolomics Reveals the Abnormal Brain Glucose Catabolism in Depression Based on Chronic Unpredictable Mild Stress Rats

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