Effects of Antemortem and Postmortem Variables on Human Brain mRNA Quality: A BrainNet Europe Study

Durrenberger, Pascal F.; Fernando, Shama; Kashefi, Samira N.; Ferrer, Isidro; Hauw, Jean-Jacques; Seilhean, Danielle; Smith, Colin; Walker, Robert; Al-Sarraj, Safa; Troakes, Claire; Palkovits, Miklos; Kasztner, Magdalena; Huitinga, Inge; Arzberger, Thomas; Dexter, David T.; Kretzschmar, Hans; Reynolds, Richard

doi:10.1097/nen.0b013e3181c7e32f

Cited by 161Molecular Biology Techniques and ApplicationsRNA Research and SplicingSingle-cell and spatial transcriptomics

Effects of Antemortem and Postmortem Variables on Human Brain mRNA Quality: A BrainNet Europe Study

Durrenberger, Pascal F., Fernando, Shama, Kashefi, Samira N., Ferrer, Isidro, Hauw, Jean-Jacques, Seilhean, Danielle, Smith, Colin, Walker, Robert +9 more·2010·Journal of Neuropathology & Experimental Neurology

DOI 10.1097/nen.0b013e3181c7e32f

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Abstract

Well-characterized and preserved human brain tissue that is prepared and stored in brain banks is an essential resource for research in neurological diseases. This study examined the quality of human brain postmortem tissue from multiple laboratories within the BrainNet Europe brain bank network to identify all possible confounding variables and determine how they may affect RNA quality. Antemortem and postmortem information was retrospectively collected for a large cohort of samples. Total RNA was isolated from anatomically defined brain regions using a standardized procedure; RNA quality was assessed using an Agilent 2100 Bioanalyzer. No significant difference in RNA quality was observed in 6 different brain regions. RNA quality deteriorated with increasing numbers of antemortem events such as hospitalization, coma, respiratory illness, and the use of artificial ventilation; accumulation of such events was associated with elevated hypoxia-inducible factor 1 alpha mRNA expression. Brain pH was found to be a good indicator of RNA quality. There was no correlation of postmortem delay with cerebrospinal fluid pH or RNA quality overall, but some individual RNAs decreased in quality with antemortem events and with postmortem delay. RNA quality did not affect total RNA yield. Determining the factors that are best predictors of RNA quality can help brain banks with selection criteria for storing high-quality brain tissue for research.

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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.”
From Dissection of artifactual and confounding glial signatures by single-cell sequencing of mouse and human brain (2022) · cites this paper as [76]
Postmortem delay (PMD) had little effect on microglial gene expression.
“These findings confirm that highly pure populations of microglia were collected and that PMD had little effect on gene expression.”
From Transcriptomic analysis of purified human cortical microglia reveals age-associated changes (2017) · cites this paper as [20]

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Postmortem Brain: An Underutilized Substrate for Studying Severe Mental Illness
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Exosomal secretion of a psychosis-altered miRNA that regulates glutamate receptor expression is affected by antipsychotics
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Metabolomics and neuroanatomical evaluation of post-mortem changes in the hippocampus
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Quantitative analysis of human endogenous retrovirus-K transcripts in postmortem premotor cortex fails to confirm elevated expression of HERV-K RNA in amyotrophic lateral sclerosis
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Using Autopsy Brain Tissue to Study Alcohol-Related Brain Damage in the Genomic Age
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Synapses, Microglia, and Lipids in Alzheimer’s Disease
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The NSW brain tissue resource centre: Banking for alcohol and major neuropsychiatric disorders research
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SIRT1 is increased in affected brain regions and hypothalamic metabolic pathways are altered in Huntington disease
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Aromatase Expression in the Hippocampus of AD Patients and 5xFAD Mice
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Early white matter pathology in the fornix of the limbic system in Huntington disease
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Analysis of RNA Expression Profiles Identifies Dysregulated Vesicle Trafficking Pathways in Creutzfeldt-Jakob Disease
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Altered Mitochondria, Protein Synthesis Machinery, and Purine Metabolism Are Molecular Contributors to the Pathogenesis of Creutzfeldt–Jakob Disease
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Genomic Positional Dissection of RNA Editomes in Tumor and Normal Samples
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Effects of Postmortem Interval and Preservation Method on RNA Isolated from Field-Preserved Avian Tissues
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Modulators of Cytoskeletal Reorganization in CA1 Hippocampal Neurons Show Increased Expression in Patients at Mid-Stage Alzheimer's Disease
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The Department of Veterans Affairs Biorepository Brain Bank: A national resource for amyotrophic lateral sclerosis research
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Translational Research in Pediatrics IV: Solid Tissue Collection and Processing
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Authors: Durrenberger, P. F., Fernando, S., Kashefi, S. N., Ferrer, I., Hauw, J.-J., Seilhean, D., Smith, C., Walker, R., Al-Sarraj, S., Troakes, C., Palkovits, M., Kasztner, M., Huitinga, I., Arzberger, T., Dexter, D. T., Kretzschmar, H., & Reynolds, R.
Affiliations: Imperial College London (GB)
Université Pierre-et-Marie-Curie (FR)
University of Edinburgh (GB)
King's College London (GB)
Semmelweis University (HU)
Netherlands Brain Bank (NL)
Institut für Neuropathologie (DE)
Corresponding author: Durrenberger, Pascal F.
ORCID: Durrenberger, Pascal F.
Hauw, Jean-Jacques
Seilhean, Danielle
Smith, Colin
Walker, Robert
Troakes, Claire
Huitinga, Inge
Dexter, David T.
Reynolds, Richard
Venue: Journal of Neuropathology & Experimental Neurology
Publisher: Oxford University Press (OUP)
Published: 2010-01
Volume: 69
Issue: 1
Pages: 70-81
ISSN: 0022-3069 (ISSN-L)
1554-6578
DOI: 10.1097/nen.0b013e3181c7e32f
OpenAlex: W2148650719
Cited by: 161
References: 53
Citations by year: 2026: 5 · 2025: 4 · 2024: 10 · 2023: 1 · 2022: 6 · 2021: 13 · 2020: 7 · 2019: 10 · 2018: 13 · 2017: 10 · 2016: 9 · 2015: 12 · 2014: 12 · 2013: 14 · 2012: 13
FWCI: 4.70
Type: journal article
Language: en
Open access: closed
Locations: Journal of Neuropathology & Experimental Neurology (publishedVersion)
PubMed (publishedVersion)
KNAW Research Portal (The Royal Netherlands Academy of Arts and Sciences) (publishedVersion)
Data Archiving and Networked Services (DANS) (submittedVersion)
KNAW research portal (Royal Academy of Art and Sciences (KNAW)) (submittedVersion)
Funders: Parkinson's UK (G0909)
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: human brain tissue, RNA quality, brain banks, postmortem delay, brain pH, hypoxia-inducible factor-1α, cerebrospinal fluid pH, brain regions, RNA yield
MeSH terms: Aged, Aged, 80 and over, Brain, Europe, Female, Humans, Male, Middle Aged, Nervous System Diseases, Organ Preservation, Postmortem Changes, RNA, Messenger, Time Factors, Tissue Banks, Cohort Studies, Linear Models, Reverse Transcriptase Polymerase Chain Reaction

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Effects of Antemortem and Postmortem Variables on Human Brain mRNA Quality: A BrainNet Europe Study

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