Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
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
_version_ 1783614886602866688
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
work_keys_str_mv AT scholefieldmelissa effectsofalterationsofpostmortemdelayandothertissuecollectionvariablesonmetabolitelevelsinhumanandratbrain
AT churchstephaniej effectsofalterationsofpostmortemdelayandothertissuecollectionvariablesonmetabolitelevelsinhumanandratbrain
AT xujingshu effectsofalterationsofpostmortemdelayandothertissuecollectionvariablesonmetabolitelevelsinhumanandratbrain
AT robinsonandrewc effectsofalterationsofpostmortemdelayandothertissuecollectionvariablesonmetabolitelevelsinhumanandratbrain
AT gardinernataliej effectsofalterationsofpostmortemdelayandothertissuecollectionvariablesonmetabolitelevelsinhumanandratbrain
AT roncarolifederico effectsofalterationsofpostmortemdelayandothertissuecollectionvariablesonmetabolitelevelsinhumanandratbrain
AT hoopernigelm effectsofalterationsofpostmortemdelayandothertissuecollectionvariablesonmetabolitelevelsinhumanandratbrain
AT unwinrichardd effectsofalterationsofpostmortemdelayandothertissuecollectionvariablesonmetabolitelevelsinhumanandratbrain
AT coopergarthjs effectsofalterationsofpostmortemdelayandothertissuecollectionvariablesonmetabolitelevelsinhumanandratbrain