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Metabolites
Volume 10
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10.3390/metabo10110438
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Article

Effects of Alterations of Post-Mortem Delay and Other Tissue-Collection Variables on Metabolite Levels in Human and Rat Brain

by
Melissa Scholefield
1,*,
Stephanie J. Church
1,
Jingshu Xu
1,2,
Andrew C. Robinson
3,
Natalie J. Gardiner
4,
Federico Roncaroli
5,
Nigel M. Hooper
6,
Richard D. Unwin
1,7 and
Garth J. S. Cooper
1,2
1
Centre 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, UK
2
School of Biological Sciences, Faculty of Science, University of Auckland, Private Bag 92 019, Auckland 1142, New Zealand
3
Division of Neuroscience & Experimental Psychology, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Salford Royal Hospital, Salford M6 8HD, UK
4
Division 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, UK
5
Division 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, UK
6
Division 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, UK
7
Stoller Biomarker Discovery Centre & Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Citylabs 1.0 (Third Floor), Nelson Street, Manchester M13 9NQ, UK
*
Author to whom correspondence should be addressed.
Metabolites 2020, 10(11), 438; https://doi.org/10.3390/metabo10110438
Submission received: 4 September 2020 / Revised: 20 October 2020 / Accepted: 27 October 2020 / Published: 29 October 2020
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Abstract

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.
Keywords: Alzheimer’s disease; post-mortem delay; human brain metabolomics; rat brain metabolomics; mass spectrometry; brain tissue quality Alzheimer’s disease; post-mortem delay; human brain metabolomics; rat brain metabolomics; mass spectrometry; brain tissue quality

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MDPI and ACS Style

Scholefield, M.; Church, S.J.; Xu, J.; Robinson, A.C.; Gardiner, N.J.; Roncaroli, F.; Hooper, N.M.; Unwin, R.D.; Cooper, G.J.S. Effects of Alterations of Post-Mortem Delay and Other Tissue-Collection Variables on Metabolite Levels in Human and Rat Brain. Metabolites 2020, 10, 438. https://doi.org/10.3390/metabo10110438

AMA Style

Scholefield M, Church SJ, Xu J, Robinson AC, Gardiner NJ, Roncaroli F, Hooper NM, Unwin RD, Cooper GJS. Effects of Alterations of Post-Mortem Delay and Other Tissue-Collection Variables on Metabolite Levels in Human and Rat Brain. Metabolites. 2020; 10(11):438. https://doi.org/10.3390/metabo10110438

Chicago/Turabian Style

Scholefield, Melissa, Stephanie J. Church, Jingshu Xu, Andrew C. Robinson, Natalie J. Gardiner, Federico Roncaroli, Nigel M. Hooper, Richard D. Unwin, and Garth J. S. Cooper. 2020. "Effects of Alterations of Post-Mortem Delay and Other Tissue-Collection Variables on Metabolite Levels in Human and Rat Brain" Metabolites 10, no. 11: 438. https://doi.org/10.3390/metabo10110438

APA Style

Scholefield, M., Church, S. J., Xu, J., Robinson, A. C., Gardiner, N. J., Roncaroli, F., Hooper, N. M., Unwin, R. D., & Cooper, G. J. S. (2020). Effects of Alterations of Post-Mortem Delay and Other Tissue-Collection Variables on Metabolite Levels in Human and Rat Brain. Metabolites, 10(11), 438. https://doi.org/10.3390/metabo10110438

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