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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7694048/ https://www.ncbi.nlm.nih.gov/pubmed/33138273 http://dx.doi.org/10.3390/metabo10110438 |
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author | Scholefield, Melissa Church, Stephanie J. Xu, Jingshu Robinson, Andrew C. Gardiner, Natalie J. Roncaroli, Federico Hooper, Nigel M. Unwin, Richard D. Cooper, Garth J. S. |
author_facet | Scholefield, Melissa Church, Stephanie J. Xu, Jingshu Robinson, Andrew C. Gardiner, Natalie J. Roncaroli, Federico Hooper, Nigel M. Unwin, Richard D. Cooper, Garth J. S. |
author_sort | Scholefield, Melissa |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-7694048 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-76940482020-11-28 Effects of Alterations of Post-Mortem Delay and Other Tissue-Collection Variables on Metabolite Levels in Human and Rat Brain Scholefield, Melissa Church, Stephanie J. Xu, Jingshu Robinson, Andrew C. Gardiner, Natalie J. Roncaroli, Federico Hooper, Nigel M. Unwin, Richard D. Cooper, Garth J. S. Metabolites Article 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. MDPI 2020-10-29 /pmc/articles/PMC7694048/ /pubmed/33138273 http://dx.doi.org/10.3390/metabo10110438 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Scholefield, Melissa Church, Stephanie J. Xu, Jingshu Robinson, Andrew C. Gardiner, Natalie J. Roncaroli, Federico Hooper, Nigel M. Unwin, Richard D. Cooper, Garth J. S. Effects of Alterations of Post-Mortem Delay and Other Tissue-Collection Variables on Metabolite Levels in Human and Rat Brain |
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 | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7694048/ https://www.ncbi.nlm.nih.gov/pubmed/33138273 http://dx.doi.org/10.3390/metabo10110438 |
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