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      Neuropsychiatric Disease and Treatment (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on all aspects of neuropsychiatric and neurological disorders. Sign up for email alerts here.

      63,741 Monthly downloads/views I 2.989 Impact Factor I 4.5 CiteScore I 1.09 Source Normalized Impact per Paper (SNIP) I 0.744 Scimago Journal & Country Rank (SJR)

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      Metabonomics reveals peripheral and central short-chain fatty acid and amino acid dysfunction in a naturally occurring depressive model of macaques

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          Abstract

          Purpose

          Depression is a complex psychiatric disorder. Various depressive rodent models are usually constructed based on different pathogenesis hypotheses.

          Materials and methods

          Herein, using our previously established naturally occurring depressive (NOD) model in a non-human primate (cynomolgus monkey, Macaca fascularis), we performed metabolomics analysis of cerebrospinal fluid (CSF) from NOD female macaques (N=10) and age-and gender-matched healthy controls (HCs) (N=12). Multivariate statistical analysis was used to identify the differentially expressed metabolites between the two groups. Ingenuity Pathways Analysis and MetaboAnalyst were applied for predicted pathways and biological functions analysis.

          Results

          Totally, 37 metabolites responsible for discriminating the two groups were identified. The NOD macaques were mainly characterized by perturbations of fatty acid biosynthesis, ABC transport system, and amino acid metabolism (eg, aspartate, glycine, serine, and threonine metabolism). Interestingly, we found that eight altered CSF metabolites belonging to short-chain fatty acids and amino acids were also observed in the serum of NOD macaques (N=13 per group).

          Conclusion

          Our findings suggest that peripheral and central short-chain fatty acids and amino acids are implicated in the onset of depression.

          Most cited references45

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          TagFinder for the quantitative analysis of gas chromatography--mass spectrometry (GC-MS)-based metabolite profiling experiments.

          Alexander Luedemann, Katrin Strassburg, Alexander Erban … (2008)
          Typical GC-MS-based metabolite profiling experiments may comprise hundreds of chromatogram files, which each contain up to 1000 mass spectral tags (MSTs). MSTs are the characteristic patterns of approximately 25-250 fragment ions and respective isotopomers, which are generated after gas chromatography (GC) by electron impact ionization (EI) of the separated chemical molecules. These fragment ions are subsequently detected by time-of-flight (TOF) mass spectrometry (MS). MSTs of profiling experiments are typically reported as a list of ions, which are characterized by mass, chromatographic retention index (RI) or retention time (RT), and arbitrary abundance. The first two parameters allow the identification, the later the quantification of the represented chemical compounds. Many software tools have been reported for the pre-processing, the so-called curve resolution and deconvolution, of GC-(EI-TOF)-MS files. Pre-processing tools generate numerical data matrices, which contain all aligned MSTs and samples of an experiment. This process, however, is error prone mainly due to (i) the imprecise RI or RT alignment of MSTs and (ii) the high complexity of biological samples. This complexity causes co-elution of compounds and as a consequence non-selective, in other words impure MSTs. The selection and validation of optimal fragment ions for the specific and selective quantification of simultaneously eluting compounds is, therefore, mandatory. Currently validation is performed in most laboratories under human supervision. So far no software tool supports the non-targeted and user-independent quality assessment of the data matrices prior to statistical analysis. TagFinder may fill this gap. TagFinder facilitates the analysis of all fragment ions, which are observed in GC-(EI-TOF)-MS profiling experiments. The non-targeted approach allows the discovery of novel and unexpected compounds. In addition, mass isotopomer resolution is maintained by TagFinder processing. This feature is essential for metabolic flux analyses and highly useful, but not required for metabolite profiling. Whenever possible, TagFinder gives precedence to chemical means of standardization, for example, the use of internal reference compounds for retention time calibration or quantitative standardization. In addition, external standardization is supported for both compound identification and calibration. The workflow of TagFinder comprises, (i) the import of fragment ion data, namely mass, time and arbitrary abundance (intensity), from a chromatography file interchange format or from peak lists provided by other chromatogram pre-processing software, (ii) the annotation of sample information and grouping of samples into classes, (iii) the RI calculation, (iv) the binning of observed fragment ions of equal mass from different chromatograms into RI windows, (v) the combination of these bins, so-called mass tags, into time groups of co-eluting fragment ions, (vi) the test of time groups for intensity correlated mass tags, (vii) the data matrix generation and (viii) the extraction of selective mass tags supported by compound identification. Thus, TagFinder supports both non-targeted fingerprinting analyses and metabolite targeted profiling. Exemplary TagFinder workspaces and test data sets are made available upon request to the contact authors. TagFinder is made freely available for academic use from http://www-en.mpimp-golm.mpg.de/03-research/researchGroups/01-dept1/Root_Metabolism/smp/TagFinder/index.html.
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            Identification and validation of urinary metabolite biomarkers for major depressive disorder.

            Peng Zheng, Ying Wang, Liang Chen … (2013)
            Major depressive disorder (MDD) is a widespread and debilitating mental disorder. However, there are no biomarkers available to aid in the diagnosis of this disorder. In this study, a nuclear magnetic resonance spectroscopy-based metabonomic approach was employed to profile urine samples from 82 first-episode drug-naïve depressed subjects and 82 healthy controls (the training set) in order to identify urinary metabolite biomarkers for MDD. Then, 44 unselected depressed subjects and 52 healthy controls (the test set) were used to independently validate the diagnostic generalizability of these biomarkers. A panel of five urinary metabolite biomarkers-malonate, formate, N-methylnicotinamide, m-hydroxyphenylacetate, and alanine-was identified. This panel was capable of distinguishing depressed subjects from healthy controls with an area under the receiver operating characteristic curve (AUC) of 0.81 in the training set. Moreover, this panel could classify blinded samples from the test set with an AUC of 0.89. These findings demonstrate that this urinary metabolite biomarker panel can aid in the future development of a urine-based diagnostic test for MDD.
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              Lipid alterations in lipid rafts from Alzheimer's disease human brain cortex.

              Gabriel Santpere, Raquel Marin, Isidre Ferrer … (2009)
              Lipid rafts are membrane microdomains intimately associated with cell signaling. These biochemical microstructures are characterized by their high contents of sphingolipids, cholesterol and saturated fatty acids and a reduced content of polyunsaturated fatty acids (PUFA). Here, we have purified lipid rafts of human frontal brain cortex from normal and Alzheimer's disease (AD) and characterized their biochemical lipid composition. The results revealed that lipid rafts from AD brains exhibit aberrant lipid profiles compared to healthy brains. In particular, lipid rafts from AD brains displayed abnormally low levels of n-3 long chain polyunsaturated fatty acids (LCPUFA, mainly 22:6n-3, docosahexaenoic acid) and monoenes (mainly 18:1n-9, oleic acid), as well as reduced unsaturation and peroxidability indexes. Also, multiple relationships between phospholipids and fatty acids were altered in AD lipid rafts. Importantly, no changes were observed in the mole percentage of lipid classes and fatty acids in rafts from normal brains throughout the lifespan (24-85 years). These indications point to the existence of homeostatic mechanisms preserving lipid raft status in normal frontal cortex. The disruption of such mechanisms in AD brains leads to a considerable increase in lipid raft order and viscosity, which may explain the alterations in lipid raft signaling observed in AD.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Neuropsychiatr Dis Treat
                Journal ID (iso-abbrev): Neuropsychiatr Dis Treat
                Journal ID (publisher-id): Neuropsychiatric Disease and Treatment
                Title: Neuropsychiatric Disease and Treatment
                Publisher: Dove Medical Press
                ISSN (Print): 1176-6328
                ISSN (Electronic): 1178-2021
                Publication date Collection: 2019
                Publication date (Electronic): 01 May 2019
                Volume: 15
                Pages: 1077-1088
                Affiliations
                [1 ]Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing 402460, People’s Republic of China, xiepeng@ 123456cqmu.edu.cn
                [2 ]Chongqing Key Laboratory of Neurobiology, Chongqing 400016, People’s Republic of China, xiepeng@ 123456cqmu.edu.cn
                [3 ]Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, People’s Republic of China, xiepeng@ 123456cqmu.edu.cn
                [4 ]School of Public Health and Management, Chongqing Medical University, Chongqing 400016, People’s Republic of China
                [5 ]The First Affiliated Hospital of Kunming Medical University, Kunming 650032, People’s Republic of China
                [6 ]Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, People’s Republic of China
                [7 ]Department of Neurology, Three Gorges Central Hospital, Chongqing Medical University, Chongqing 400016, People’s Republic of China
                Author notes
                Correspondence: Peng Xie, Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, Chongqing 400016, People’s Republic of China, Tel +86 236 848 5490, Fax +86 236 848 5111, Email xiepeng@ 123456cqmu.edu.cn
                [*]

                These authors contributed equally to this work

                Article
                Publisher ID: ndt-15-1077
                DOI: 10.2147/NDT.S186071
                PMC ID: 6501704
                PubMed ID: 31118641
                SO-VID: 4c8ec30b-616d-4e41-b332-927c9050c4d7
                Copyright © © 2019 Deng et al. This work is published and licensed by Dove Medical Press Limited
                License:

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                History
                Categories
                Subject: Original Research

                ScienceOpen disciplines: Neurology
                Keywords: naturally occurring depressive,depression,non-human primate,metabonomics,cerebrospinal fluid,short-chain fatty acid
                Data availability:
                ScienceOpen disciplines: Neurology
                Keywords: naturally occurring depressive, depression, non-human primate, metabonomics, cerebrospinal fluid, short-chain fatty acid

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