Metabolomics studies on corticosterone-induced PC12 cells: A strategy for evaluating an in vitro depression model and revealing the metabolic regulation mechanism

Tian, Jun-Sheng; Liu, Shaobo; He, Xu; Xiang, Huan; Chen, Jianli; Gao, Yao; Zhou, Yuzhi; Qin, Xuemei

doi:10.1016/j.ntt.2018.07.002

Cited by 34 publications

(28 citation statements)

References 50 publications

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“…The metabolic networks involved in some enzymes and genes were constructed with Cytoscape to better understand the internal correlation of the potential biomarkers in terms of the enzyme or gene levels (Tian et al, 2018). The metabolic networks that were established based on the markedly different metabolites are shown in Figure 7.…”

Section: Cytoscape To Explore the Biomarker Metabolic Networkmentioning

confidence: 99%

Serum Metabolic Profiling Reveals the Antidepressive Effects of the Total Iridoids of Valeriana jatamansi Jones on Chronic Unpredictable Mild Stress Mice

Chang

et al. 2020

Front. Pharmacol.

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Background: Depression is a long-term complex psychiatric disorder, and its etiology remains largely unknown. Valeriana jatamansi Jones ex Roxb (V. jatamansi) is used in the clinic for the treatment of depression, but there are insufficient reports of its antidepressive mechanisms and a poor understanding of its endogenous substance-related metabolism. The objective of this study was to identify biomarkers related to depression in serum samples and evaluate the antidepressive effects of the iridoid-rich fraction of V. jatamansi (IRFV) in a chronic unpredictable mild stress (CUMS) mouse model. Methods: Here, CUMS was used to establish a mouse model of depression. Behavioral and biochemical indicators were investigated to evaluate the pharmacodynamic effects. A comprehensive serum metabolomics study by nuclear magnetic resonance (NMR) approach was applied to investigate the pharmacological mechanism of IRFV in CUMS mouse. Subsequently, we used multivariate statistical analysis to identify metabolic markers, such as principal component analysis (PCA) and orthogonal projection to latent structure with discriminant analysis (OPLS-DA), to distinguish between the CUMS mouse and the control group. Results: After IRFV treatment, the immobility time, sucrose preference, and monoamine neurotransmitter were improved. PCA scores showed clear differences in metabolism between the CUMS group and control group. The PLS-DA or OPLS-DA model exhibited 26 metabolites as biomarkers to distinguish between the CUMS mice and the control mouse. Moreover, IRFV could significantly return 21 metabolites to normal levels. Conclusion: The results confirmed that IRFV exerted an antidepressive effect by regulating multiple metabolic pathways, including the tricarboxylic acid cycle, the synthesis of neurotransmitters, and amino acid metabolism. These findings provide insights into the antidepressive mechanisms of IRFV.

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Section: Cytoscape To Explore the Biomarker Metabolic Networkmentioning

confidence: 99%

Serum Metabolic Profiling Reveals the Antidepressive Effects of the Total Iridoids of Valeriana jatamansi Jones on Chronic Unpredictable Mild Stress Mice

Chang

et al. 2020

Front. Pharmacol.

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“…Given to the 24 h-treatment of 200 μmol/L CORT decreased cell viability significantly (Fig. 1b), a cytotoxicity-free dosage of CORT (100 μmol/L) was used for cell modeling [49].…”

Section: Cell Viability With Bbr or Cort Administrationmentioning

confidence: 99%

Proteomic profiling of the neurons in mice with depressive-like behavior induced by corticosterone and the regulation of berberine: pivotal sites of oxidative phosphorylation

et al. 2019

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Chronic corticosterone (CORT) stress is an anxiety and depression inducing factor that involves the dysfunction of glucocorticoid receptor (GR), brain-derived neurotrophic factor (BDNF), and neuronal plasticity. However, the regulation of proteomic profiles in neurons suffering CORT stress is remaining elusive. Thus, the proteomic profiles of mouse neuronal C17.2 stem cells were comprehensively investigated by TMT (tandem mass tag)-labeling quantitative proteomics. The quantitative proteomics conjugated gene ontology analysis revealed the inhibitory effect of CORT on the expression of mitochondrial oxidative phosphorylation-related proteins, which can be antagonized by berberine (BBR) treatment. In addition, animal studies showed that changes in mitochondria by CORT can affect neuropsychiatric activities and disturb the physiological functions of neurons via disordering mitochondrial oxidative phosphorylation. Thus, the mitochondrial energy metabolism can be considered as one of the major mechanism underlying CORT-mediated depression. Since CORT is important for depression after traumatic stress disorder, our study will shed light on the prevention and treatment of depression as well as posttraumatic stress disorder (PTSD).

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“…PC12 cells are used commonly for the establishment of depression models in vitro when they are combined with the administration of CORT 19. To obtain an appropriate depression model, PC12 cells were treated with different concentrations of CORT.…”

Section: Resultsmentioning

confidence: 99%

Leonurine promotes neurite outgrowth and neurotrophic activity by modulating the GR/SGK1 signaling pathway in cultured PC12 cells

et al. 2019

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Depression is a common psychiatric disorder that affects almost 10% of children and adolescents worldwide. Numerous synthetic chemical antidepressants used to treat depression have adverse side effects. Therefore, new therapeutic approaches for depression treatment are urgently needed. Leonurus cardiaca has recently been shown to be effective for the treatment of nervous system diseases such as depression, but its mechanism is not clear. In this study, we aimed to reveal the mechanism underlying leonurine’s antidepressant activity. Leonurine was used to treat corticosterone-induced PC12 cells to examine its effect on neurite outgrowth and neurotrophic factors after treatment with the inhibitor of glucocorticoid receptor (GR) and serum-inducible and glucocorticoid-inducible kinase 1 (SGK1). Methyl thiazolyl tetrazolium assays were used to evaluate the viability of cells. High content analysis was used to detect cell area, total neurite length, maximum neurite length, and expression of GR, SGK1, brain-derived neurotrophic factor (BDNF), neurotrophic factor-3 (NT-3), and B-cell lymphoma-2 (BCL-2). The results showed that leonurine increased cell viability in a concentration-dependent manner, with the maximal prosurvival effect at 60 μM. Leonurine increased cell area, total neurite length, and maximum neurite length of corticosterone-induced PC12 cells, increased the expression of GR, BDNF, NT-3, and BCL-2, and decreased the expression of SGK1. After treatment with GR inhibitor RU486, the expressions of GR, BDNF, NT-3, and BCL-2 were significantly decreased and SGK1 was increased. In contrast, treatment with GSK650394 had the opposite effect of RU486. Our data indicate that leonurine promotes neurite outgrowth and neurotrophic activity in cultured PC12 cells, and its potential mechanism may involve the GR/SGK1 signaling pathway.

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Metabolomics studies on corticosterone-induced PC12 cells: A strategy for evaluating an in vitro depression model and revealing the metabolic regulation mechanism

Cited by 34 publications

References 50 publications

Serum Metabolic Profiling Reveals the Antidepressive Effects of the Total Iridoids of Valeriana jatamansi Jones on Chronic Unpredictable Mild Stress Mice

Serum Metabolic Profiling Reveals the Antidepressive Effects of the Total Iridoids of Valeriana jatamansi Jones on Chronic Unpredictable Mild Stress Mice

Proteomic profiling of the neurons in mice with depressive-like behavior induced by corticosterone and the regulation of berberine: pivotal sites of oxidative phosphorylation

Leonurine promotes neurite outgrowth and neurotrophic activity by modulating the GR/SGK1 signaling pathway in cultured PC12 cells

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