Effects of Alterations of Post-Mortem Delay and Other Tissue-Collection Variables on Metabolite Levels in Human and Rat Brain
The use of post-mortem human tissue is indispensable in studies investigating alterations in metabolite levels in neurodegenerative conditions such as Alzheimer’s disease (AD). However, variability between samples may have unknown effects on metabolite concentrations. The aim of this study was to ch...
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| Format: | Article |
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MDPI AG
2020-10-01
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| Series: | Metabolites |
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| Online Access: | https://www.mdpi.com/2218-1989/10/11/438 |
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| author | Melissa Scholefield Stephanie J. Church Jingshu Xu Andrew C. Robinson Natalie J. Gardiner Federico Roncaroli Nigel M. Hooper Richard D. Unwin Garth J. S. Cooper |
| author_facet | Melissa Scholefield Stephanie J. Church Jingshu Xu Andrew C. Robinson Natalie J. Gardiner Federico Roncaroli Nigel M. Hooper Richard D. Unwin Garth J. S. Cooper |
| author_sort | Melissa Scholefield |
| collection | DOAJ |
| description | The use of post-mortem human tissue is indispensable in studies investigating alterations in metabolite levels in neurodegenerative conditions such as Alzheimer’s disease (AD). However, variability between samples may have unknown effects on metabolite concentrations. The aim of this study was to characterize the impact of such variables. Cingulate gyrus was obtained from AD cases and controls, from three brain banks. Gas chromatography-mass spectrometry (GC-MS) was used to measure and compare the levels of 66 identifiable metabolites in these tissues to determine effects of tissue-collection variables. The effect of PMD was further investigated by analysis of rat brain cortex and cerebellum collected following post-mortem delays (PMDs) of zero to 72 h. Metabolite levels between cases and controls were not replicable across cohorts with variable age- and gender-matching, PMD, and control Braak staging. Analysis of rat tissues found significant effects of PMD on 31 of 63 identified metabolites over periods up to 72 h. PMD must be kept under 24 h for metabolomics analyses on brain tissues to yield replicable results. Tissues should also be well age- and gender-matched, and Braak stage in controls should be kept to a minimum in order to minimize the impact of these variables in influencing metabolite variability. |
| first_indexed | 2024-03-10T15:14:13Z |
| format | Article |
| id | doaj.art-bd6bf168e484432ab371cc420f223056 |
| institution | Directory Open Access Journal |
| issn | 2218-1989 |
| language | English |
| last_indexed | 2024-03-10T15:14:13Z |
| publishDate | 2020-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Metabolites |
| spelling | doaj.art-bd6bf168e484432ab371cc420f2230562023-11-20T19:05:58ZengMDPI AGMetabolites2218-19892020-10-01101143810.3390/metabo10110438Effects of Alterations of Post-Mortem Delay and Other Tissue-Collection Variables on Metabolite Levels in Human and Rat BrainMelissa Scholefield0Stephanie J. Church1Jingshu Xu2Andrew C. Robinson3Natalie J. Gardiner4Federico Roncaroli5Nigel M. Hooper6Richard D. Unwin7Garth J. S. Cooper8Centre for Advanced Discovery & Experimental Therapeutics, Division of Cardiovascular Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, Manchester M19 9NT, UKCentre for Advanced Discovery & Experimental Therapeutics, Division of Cardiovascular Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, Manchester M19 9NT, UKCentre for Advanced Discovery & Experimental Therapeutics, Division of Cardiovascular Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, Manchester M19 9NT, UKDivision of Neuroscience & Experimental Psychology, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Salford Royal Hospital, Salford M6 8HD, UKDivision of Diabetes, Endocrinology & Gastroenterology, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, Oxford Rd, Manchester M13 9PL, UKDivision of Neuroscience & Experimental Psychology, and Lydia Becker Institute of Immunology & Inflammation, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, Manchester M19 9NT, UKDivision of Neuroscience & Experimental Psychology, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, Manchester M19 9NT, UKCentre for Advanced Discovery & Experimental Therapeutics, Division of Cardiovascular Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, Manchester M19 9NT, UKCentre for Advanced Discovery & Experimental Therapeutics, Division of Cardiovascular Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, Manchester M19 9NT, UKThe use of post-mortem human tissue is indispensable in studies investigating alterations in metabolite levels in neurodegenerative conditions such as Alzheimer’s disease (AD). However, variability between samples may have unknown effects on metabolite concentrations. The aim of this study was to characterize the impact of such variables. Cingulate gyrus was obtained from AD cases and controls, from three brain banks. Gas chromatography-mass spectrometry (GC-MS) was used to measure and compare the levels of 66 identifiable metabolites in these tissues to determine effects of tissue-collection variables. The effect of PMD was further investigated by analysis of rat brain cortex and cerebellum collected following post-mortem delays (PMDs) of zero to 72 h. Metabolite levels between cases and controls were not replicable across cohorts with variable age- and gender-matching, PMD, and control Braak staging. Analysis of rat tissues found significant effects of PMD on 31 of 63 identified metabolites over periods up to 72 h. PMD must be kept under 24 h for metabolomics analyses on brain tissues to yield replicable results. Tissues should also be well age- and gender-matched, and Braak stage in controls should be kept to a minimum in order to minimize the impact of these variables in influencing metabolite variability.https://www.mdpi.com/2218-1989/10/11/438Alzheimer’s diseasepost-mortem delayhuman brain metabolomicsrat brain metabolomicsmass spectrometrybrain tissue quality |
| spellingShingle | Melissa Scholefield Stephanie J. Church Jingshu Xu Andrew C. Robinson Natalie J. Gardiner Federico Roncaroli Nigel M. Hooper Richard D. Unwin Garth J. S. Cooper Effects of Alterations of Post-Mortem Delay and Other Tissue-Collection Variables on Metabolite Levels in Human and Rat Brain Metabolites Alzheimer’s disease post-mortem delay human brain metabolomics rat brain metabolomics mass spectrometry brain tissue quality |
| title | Effects of Alterations of Post-Mortem Delay and Other Tissue-Collection Variables on Metabolite Levels in Human and Rat Brain |
| title_full | Effects of Alterations of Post-Mortem Delay and Other Tissue-Collection Variables on Metabolite Levels in Human and Rat Brain |
| title_fullStr | Effects of Alterations of Post-Mortem Delay and Other Tissue-Collection Variables on Metabolite Levels in Human and Rat Brain |
| title_full_unstemmed | Effects of Alterations of Post-Mortem Delay and Other Tissue-Collection Variables on Metabolite Levels in Human and Rat Brain |
| title_short | Effects of Alterations of Post-Mortem Delay and Other Tissue-Collection Variables on Metabolite Levels in Human and Rat Brain |
| title_sort | effects of alterations of post mortem delay and other tissue collection variables on metabolite levels in human and rat brain |
| topic | Alzheimer’s disease post-mortem delay human brain metabolomics rat brain metabolomics mass spectrometry brain tissue quality |
| url | https://www.mdpi.com/2218-1989/10/11/438 |
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