The relative importance of premortem acidosis and postmortem interval for human brain gene expression studies: selective mRNA vulnerability and comparison with their encoded proteins

Harrison, P.J.; Heath, P.R.; Eastwood, S.L.; Burnet, P.W.J.; McDonald, B.; Pearson, R.C.A.

doi:10.1016/0304-3940(95)12102-a

Cited by 342Molecular Biology Techniques and ApplicationsRNA Research and SplicingSingle-cell and spatial transcriptomics

The relative importance of premortem acidosis and postmortem interval for human brain gene expression studies: selective mRNA vulnerability and comparison with their encoded proteins

Harrison, P.J., Heath, P.R., Eastwood, S.L., Burnet, P.W.J., McDonald, B., Pearson, R.C.A.·1995·Neuroscience Letters

DOI 10.1016/0304-3940(95)12102-a

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Abstract

To help account for the variable quality and quantity of RNA in human brain, we have studied the effect of premortem (agonal state) and postmortem factors on the detection of poly(A)+mRNA and eight mRNAs. For comparison, the influence of the same factors upon gene products encoded by the mRNAs was studied immunocytochemically or by receptor autoradiography. Brain pH declined with increasing age at death and was related to agonal state severity, but was independent of postmortem interval and the histological presence of hypoxic changes. By linear regression, pH was significantly associated with the abundance of several of the RNAs, but not with poly(A)+mRNA, immunoreactivities, or binding site densities. Postmortem interval had a limited influence upon mRNA and protein products. Freezer storage time showed no effect. Parallel rat brain studies showed no relationship between postmortem interval (0-48 h) and amounts of total RNA, poly(A)+RNA, or two individual mRNAs; however, RNA content was reduced by 40% at 96 h after death. pH is superior to clinical assessments of agonal state or mode of death in predicting mRNA preservation. It provides a simple means to improve human brain gene expression studies. pH is stable after death and during freezer storage and can be measured either in cerebrospinal fluid or in homogenised tissue.

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Very few transcriptomic studies provide information on acute premortem variables or cause of death, which may potentially have a much larger effect on RNA quality and gene expression.
“Additionally, very few transcriptomic studies provide information on acute premortem variables or cause of death, which are particularly important as they may potentially have a much larger effect on RNA quality and gene expression71–76,78–80.”
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Authors: Harrison, P. J., Heath, P. R., Eastwood, S. L., Burnet, P. W. J., McDonald, B., & Pearson, R. C. A.
Affiliations: University of Oxford (GB)
University of Sheffield (GB)
Corresponding author: Harrison, P.J.
ORCID: Harrison, P.J.
Heath, P.R.
Burnet, P.W.J.
Venue: Neuroscience Letters
Publisher: Elsevier BV
Published: 1995-11
Volume: 200
Issue: 3
Pages: 151-154
ISSN: 0304-3940 (ISSN-L)
DOI: 10.1016/0304-3940(95)12102-a
OpenAlex: W2090829912
Cited by: 342
References: 23
Citations by year: 2026: 3 · 2025: 1 · 2024: 9 · 2023: 7 · 2022: 6 · 2021: 7 · 2020: 4 · 2019: 4 · 2018: 12 · 2017: 5 · 2016: 6 · 2015: 6 · 2014: 8 · 2013: 10 · 2012: 16
FWCI: 1.84
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Neuroscience Letters (publishedVersion)
PubMed (publishedVersion)
Funders: Wellcome Trust
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Molecular Biology Techniques and Applications
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
Keywords: postmortem interval, agonal state, brain pH, polyadenylated RNA, receptor binding
MeSH terms: Acidosis, Adolescent, Adult, Aged, Aged, 80 and over, Autoradiography, Brain Chemistry, Female, Humans, Hydrogen-Ion Concentration, Immunohistochemistry, Male, Middle Aged, Nerve Tissue Proteins, Poly A, Postmortem Changes, RNA, Messenger, Time Factors, Gene Expression, In Situ Hybridization

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The relative importance of premortem acidosis and postmortem interval for human brain gene expression studies: selective mRNA vulnerability and comparison with their encoded proteins

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