Metabolomic Analysis Reveals Metabolic Disturbance in the Cortex and Hippocampus of Subchronic MK-801 Treated Rats

Sun, Liya; Li, Juan; Zhou, Kejun; Zhang, Ming; Yang, Jinglei; Li, Yang; Ji, Baohu; Zhao, Zi‐Gang; Zhu, Hui; Yang, Lun; He, Guang; Gao, Linghan; Wei, Zhiyun; Wang, Kejian; Han, Xue; Liu, Weiqing; Tan, Liwen; Yu, Yihua; He, Lin; Wan, Chunling

doi:10.1371/journal.pone.0060598

Cited by 27 publications

(20 citation statements)

References 47 publications

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“…Numerous studies have reported the activation of these amino acid metabolism pathways in schizophrenia. [48][49][50] Therefore, we deduced that the decreased level of fumaric acid may reflect the increase in amino acid metabolism in schizophrenia, which needs further research. These speculations concord with the well-established theory that the disturbance of energy metabolism contributes to the pathogenesis of schizophrenia.…”

Section: Discussionmentioning

confidence: 95%

GC-MS based metabolomics identification of possible novel biomarkers for schizophrenia in peripheral blood mononuclear cells

et al. 2014

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Schizophrenia is a debilitating mental disorder. Currently, the lack of disease biomarkers to support objective laboratory tests constitutes a bottleneck in the clinical diagnosis of schizophrenia. Here, a gas chromatography-mass spectrometry (GC-MS) based metabolomic approach was applied to characterize the metabolic profile of schizophrenia subjects (n = 69) and healthy controls (n = 85) in peripheral blood mononuclear cells (PBMCs) to identify and validate biomarkers for schizophrenia. Multivariate statistical analysis was used to visualize group discrimination and to identify differentially expressed metabolites in schizophrenia subjects relative to healthy controls. The multivariate statistical analysis demonstrated that the schizophrenia group was significantly distinguishable from the control group. In total, 18 metabolites responsible for the discrimination between the two groups were identified. These differential metabolites were mainly involved in energy metabolism, oxidative stress and neurotransmitter metabolism. A simplified panel of PBMC metabolites consisting of pyroglutamic acid, sorbitol and tocopherol-α was identified as an effective diagnostic tool, yielding an area under the receiver operating characteristic curve (AUC) of 0.82 in the training samples (45 schizophrenia subjects and 50 healthy controls) and 0.71 in the test samples (24 schizophrenic patients and 35 healthy controls). Taken together, these findings help to develop diagnostic tools for schizophrenia.

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Section: Discussionmentioning

confidence: 95%

GC-MS based metabolomics identification of possible novel biomarkers for schizophrenia in peripheral blood mononuclear cells

et al. 2014

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“…In schizophrenia field, metabonomics findings show systematic changes in pathways of glutamate metabolism and Krebs cycle in the cortex and hippocampus of rats treated with MK-801 [13]. Metabolomics acts as a powerful tool for detecting variations in a range of intracellular compounds upon drug exposure [14].…”

Section: Introductionmentioning

confidence: 99%

Mechanisms of Metabonomic for a Gateway Drug: Nicotine Priming Enhances Behavioral Response to Cocaine with Modification in Energy Metabolism and Neurotransmitter Level

Bu²,

Chen³

et al. 2014

PLoS ONE

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Nicotine, one of the most commonly used drugs, has become a major concern because tobacco serves as a gateway drug and is linked to illicit drug abuse, such as cocaine and marijuana. However, previous studies mainly focused on certain genes or neurotransmitters which have already been known to participate in drug addiction, lacking endogenous metabolic profiling in a global view. To further explore the mechanism by which nicotine modifies the response to cocaine, we developed two conditioned place preference (CPP) models in mice. In threshold dose model, mice were pretreated with nicotine, followed by cocaine treatment at the dose of 2 mg/kg, a threshold dose of cocaine to induce CPP in mice. In high-dose model, mice were only treated with 20 mg/kg cocaine, which induced a significant CPP. 1H nuclear magnetic resonance based on metabonomics was used to investigate metabolic profiles of the nucleus accumbens (NAc) and striatum. We found that nicotine pretreatment dramatically increased CPP induced by 2 mg/kg cocaine, which was similar to 20 mg/kg cocaine-induced CPP. Interestingly, metabolic profiles showed considerable overlap between these two models. These overlapped metabolites mainly included neurotransmitters as well as the molecules participating in energy homeostasis and cellular metabolism. Our results show that the reinforcing effect of nicotine on behavioral response to cocaine may attribute to the modification of some specific metabolites in NAc and striatum, thus creating a favorable metabolic environment for enhancing conditioned rewarding effect of cocaine. Our findings provide an insight into the effect of cigarette smoking on cocaine dependence and the underlying mechanism.

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“…We paid close attention to keeping the changes in metabolites nearly uniform between samples; accordingly, the measuring temperature was maintained at 298 K to narrow the changes in metabolites in the brain tissue caused by the change in temperature during measurement. 22) This operation was performed using VnmrJ software (Ver. 4.0; Agilent Technologies).…”

Section: H-nmr Spectroscopy Of Tissue Samples Nmr Sample Preparationmentioning

confidence: 99%

“…8.1, Chenomx Inc., Edmonton, AB, Canada) and previously reported spectra. 22,23) Multivariate Analysis For multivariate analysis of NMR-derived data, all the acquired free induction decays were zero-filled to 32 k using Alice2 for Metabolome software (Ver. 2; JEOL, Tokyo, Japan) and the absolute values were differentiated following Fourier transformation.…”

Section: H-nmr Spectroscopy Of Tissue Samples Nmr Sample Preparationmentioning

confidence: 99%

High-Resolution Magic-Angle Spinning-<sup>1</sup>H-NMR Spectroscopy-Based Metabolic Profiling of Hippocampal Tissue in Rats with Depression-Like Symptoms

Akimoto

Oshima

Ohara

et al. 2017

Biological & Pharmaceutical Bulletin

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Depressive disorders cause large socioeconomic effects influencing not only the patients themselves but also their family and broader community as well. To better understand the physiologic factors underlying depression, in this study, we performed metabolomics analysis, an omics technique that comprehensively analyzes small molecule metabolites in biological samples. Specifically, we utilized high-resolution magic-angle spinning-1 H-NMR (HRMAS-1 H-NMR) spectroscopy to comprehensively analyze the changes in metabolites in the hippocampal tissue of rats exposed to chronic stress (CS) via multi-step principal component analysis (multi-step PCA). The rats subjected to CS exhibited obvious depression-like behaviors. High correlations were observed between the first principal component (PC1) score in the score plot obtained using multi-step PCA and measurements from depression-like behavioral testing (body weight, sucrose preference test, and open field test). Alanine, glutamate, glutamine, and aspartate levels in the hippocampal tissue were significantly lower, whereas N-acetylaspartate, myo-inositol, and creatine were significantly higher in the CS group compared to the control (non-CS) group. As alanine, glutamate, and glutamine are known to be involved in energy metabolism, especially in the tricarboxylic acid cycle, chronic exogenous stress may have induced abnormalities in energy metabolism in the brains of the rats. The results suggest that N-acetylaspartate and creatine levels may have increased in order to complement the loss of energy-producing activity resulting from the development of the depression-like disorder. Multi-step PCA therefore allowed an exploration of the degree of depression-like symptoms as represented by changes in intrinsic metabolites.

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Metabolomic Analysis Reveals Metabolic Disturbance in the Cortex and Hippocampus of Subchronic MK-801 Treated Rats

Cited by 27 publications

References 47 publications

GC-MS based metabolomics identification of possible novel biomarkers for schizophrenia in peripheral blood mononuclear cells

GC-MS based metabolomics identification of possible novel biomarkers for schizophrenia in peripheral blood mononuclear cells

Mechanisms of Metabonomic for a Gateway Drug: Nicotine Priming Enhances Behavioral Response to Cocaine with Modification in Energy Metabolism and Neurotransmitter Level

High-Resolution Magic-Angle Spinning-<sup>1</sup>H-NMR Spectroscopy-Based Metabolic Profiling of Hippocampal Tissue in Rats with Depression-Like Symptoms

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