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

Authors :
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
Source :
Metabolites, Vol 10, Iss 11, p 438 (2020)
Publication Year :
2020
Publisher :
MDPI AG, 2020.

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.

Details

Language :
English
ISSN :
22181989
Volume :
10
Issue :
11
Database :
Directory of Open Access Journals
Journal :
Metabolites
Publication Type :
Academic Journal
Accession number :
edsdoj.bd6bf168e484432ab371cc420f223056
Document Type :
article
Full Text :
https://doi.org/10.3390/metabo10110438