A metabolomics-based approach for ranking the depressive level in a chronic unpredictable mild stress rat model

Yu, Xinyu; Qiao, Shubin; Wang, Di; Dai, Jiayong; Wang, Jun; Zhang, Rutan; Wang, Li; Li, Lei

doi:10.1039/c6ra00665e

Cited by 7 publications

(9 citation statements)

References 40 publications

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“…1a). immobility time in the FST (26) was clearly increased in the model group during the cuMS procedure. in the model group, caa and paroxetine treatment were significantly increased compared with the control during week 3.…”

Section: Resultsmentioning

confidence: 87%

“…a total of 40 male Wistar rats (age, 4 weeks; mean weight ± Sd, 100±10 g), were purchased from Shanghai Slac laboratory animal co., ltd. The size of cages was 460x300x160 mm and animal designs were set up as previously described (26) (Table SI; Appendices S1 and S2). Briefly, after 2 weeks of acclimatization the rats were first trained over a period of 3 weeks to consume a 1% sucrose solution.…”

Section: Methodsmentioning

confidence: 99%

“…Paroxetine and caa were administered intraperitoneally at doses of 10and 50 mg/kg for at 9:00 a.m. every day for 4 weeks, respectively. rats in the control (no treatment) and treated groups were exposed to a series of cuMS and behavioral tests, including the sucrose preference test (SPT) and the forced swimming test (FST) (26). during these tests, food consumption and body weight were evaluated as an indicator of depression as previously described (26) (data not shown).…”

Section: Methodsmentioning

confidence: 99%

“…mrna levels of dnmt1, dnmt3a, Tet1-3, methyl cpG binding protein 2 (Mecp2), Bdnf and comt genes were quantified using SYBR Green-based qPCR using 2X SYBR Green Pcr mix (Takara Biotechnology co., ltd.) according to the manufacturer's instructions. Primer sequences are listed in Table I (15,19,26). All amplifications were performed in triplicate using a lightcycler ® 96 (roche diagnostics) according to the manufacturer's instructions with the following cycle parameters: 95˚C for 600 sec, followed by 45 repeats of 95˚C for 15 sec and 60˚C for 60 sec.…”

Section: Quantification Of Mrna Levels Of Epigenetic Modulators and Smentioning

confidence: 99%

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Effects of caffeic acid on epigenetics in the brain of rats with chronic unpredictable mild stress

Cao

Zhang

et al. 2020

Mol Med Rep

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The present study hypothesized that caffeic acid (3,4-dihydroxycinnamic acid; caa) may exert antidepressant-like effects in rats with chronic unpredictable mild stress via epigenetic mechanisms, such as dna methylation and hydroxymethylation. The chronic unpredictable mild stress (cuMS) model was used to analyze the effects of caa on behavioral phenotypes, and to evaluate the distribution of 5-methylcytosine (5mc) and 5-hydroxymethylcytosine (5hmc) in the hippocampus and prefrontal cortex using immunohistochemistry and immunofluorescence. mrna levels of the genes encoding brain-derived neurotropic factor (BdnF) and catechol-o-methyltransferase (coMT), and key enzymes regulating dna methylation [dna methyltransferase (dnMT)1 and dnMT3a] and hydroxymethylation [Ten-eleven translocation (TeT)1-3] were examined using quantitative (q)Pcr. Furthermore, enrichment of 5mc and 5hmc at the promotor regions of the Bdnf and Comt genes was quantified using chromatin immunoprecipitation-qPcr. Behavioral data showed that caa exerted a slight antidepressant-like effect. Bdnf and Comt genes showed differential expression patterns due to cuMS. caa intervention induced different Dnmt1/Dnmt3a and Tet1/Tet2 mrna levels in the hippocampus and prefrontal cortex, respectively. caa regulated the ratio of 5mc/5hmc at the promotor region of the Bdnf and Comt genes and therefore influenced gene expression, which may be a valuable therapeutic option for major depressive disorder (Mdd). in conclusion, there were epigenetic changes in the hippocampus and prefrontal cortex in cuMS rats, and caa may function as a modulator of dna methylation to regulate gene transcription, thus providing a mechanistic basis for the use of this phytochemical agent in the treatment of Mdd.

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Section: Resultsmentioning

confidence: 87%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Quantification Of Mrna Levels Of Epigenetic Modulators and Smentioning

confidence: 99%

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Effects of caffeic acid on epigenetics in the brain of rats with chronic unpredictable mild stress

Cao

Zhang

et al. 2020

Mol Med Rep

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“…After centrifugation of the mixture at 12000 rpm g for 15 min at 4 °C, the supernatant fraction was collected and divided into two parts: one (300ìl) for liquid chromatography- mass spectrometry (LC-MS) analysis and one (150 ìl) for gas chromatography -mass spectrometer (GC-MS) analysis after derivatization with BSTFA (containing 1% TMCS). Serum metabolic profiling analysis by LC-MS was performed as our previous study 46 . Briefly, LC-MS analysis was performed on a Thermo Scientific Q Exactive hybrid quadrupole-orbitrap mass spectrometer coupled with a UPLC Ultimate 3000 system (Thermo Fisher Scientific, Bremen, Germany) equipped a heated electrospray source (HESI), at both positive and negative ion modes.…”

Section: Methodsmentioning

confidence: 99%

Metabolic and microbial signatures in rat hepatocellular carcinoma treated with caffeic acid and chlorogenic acid

Zhang

Wang

Qiao

et al. 2017

Sci Rep

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Hepatocellular carcinoma (HCC) treatment remains lack of effective chemopreventive agents, therefore it is very attractive and urgent to discover novel anti-HCC drugs. In the present study, the effects of chlorogenic acid (ChA) and caffeic acid (CaA) on HCC induced by diethylnitrosamine (DEN) were evaluated. ChA or CaA could reduce the histopathological changes and liver injury markers, such as alanine transarninase, aspartate aminotransferase, alkaline phosphatase, total bile acid, total cholesterol, high density lipoprotein cholesterol and low density lipoprotein cholesterol. The underlying mechanisms were investigated by a data integration strategy based on correlation analyses of metabonomics data and 16 S rRNA gene sequencing data. ChA or CaA could inhibit the increase of Rumincoccaceae UCG-004 and reduction of Lachnospiraceae incertae sedis, and Prevotella 9 in HCC rats. The principal component analysis and partial least squares discriminant analysis were applied to reveal the metabolic differences among these groups. 28 different metabolites showed a trend to return to normal in both CaA and ChA treatment. Among them, Bilirubin, L-Tyrosine, L-Methionine and Ethanolamine were correlated increased Rumincoccaceae UCG-004 and decreased of Lachnospiraceae incertae sedis and Prevotella 9. These correlations could be identified as metabolic and microbial signatures of HCC onset and potential therapeutic targets.

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Metabolomic analysis of animal models of depression

Tian

Liu

et al. 2020

Metab Brain Dis

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A metabolomics-based approach for ranking the depressive level in a chronic unpredictable mild stress rat model

Abstract: An untargeted metabolomics study to investigate the metabolome change in plasma, hippocampus and prefrontal cortex (PFC) in an animal model with a major depressive disorder (MDD) had been conducted.

Cited by 7 publications

References 40 publications

Effects of caffeic acid on epigenetics in the brain of rats with chronic unpredictable mild stress

Effects of caffeic acid on epigenetics in the brain of rats with chronic unpredictable mild stress

Metabolic and microbial signatures in rat hepatocellular carcinoma treated with caffeic acid and chlorogenic acid

Metabolomic analysis of animal models of depression

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