The influence of tissue pH and RNA integrity number on gene expression of human postmortem brain

BackgroundEvaluating and controlling confounders are necessary when investigating molecular pathogenesis using human postmortem brain tissue. Particularly, tissue pH and RNA integrity number (RIN) are valuable indicators for controlling confounders. However, the influences of these indicators on the...

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Main Authors: Kazusa Miyahara, Mizuki Hino, Zhiqian Yu, Chiaki Ono, Atsuko Nagaoka, Masataka Hatano, Risa Shishido, Hirooki Yabe, Hiroaki Tomita, Yasuto Kunii
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-07-01
Series:Frontiers in Psychiatry
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fpsyt.2023.1156524/full
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author Kazusa Miyahara
Mizuki Hino
Mizuki Hino
Zhiqian Yu
Chiaki Ono
Atsuko Nagaoka
Masataka Hatano
Risa Shishido
Hirooki Yabe
Hiroaki Tomita
Hiroaki Tomita
Yasuto Kunii
Yasuto Kunii
author_facet Kazusa Miyahara
Mizuki Hino
Mizuki Hino
Zhiqian Yu
Chiaki Ono
Atsuko Nagaoka
Masataka Hatano
Risa Shishido
Hirooki Yabe
Hiroaki Tomita
Hiroaki Tomita
Yasuto Kunii
Yasuto Kunii
author_sort Kazusa Miyahara
collection DOAJ
description BackgroundEvaluating and controlling confounders are necessary when investigating molecular pathogenesis using human postmortem brain tissue. Particularly, tissue pH and RNA integrity number (RIN) are valuable indicators for controlling confounders. However, the influences of these indicators on the expression of each gene in postmortem brain have not been fully investigated. Therefore, we aimed to assess these effects on gene expressions of human brain samples.MethodsWe isolated total RNA from occipital lobes of 13 patients with schizophrenia and measured the RIN and tissue pH. Gene expression was analyzed and gene sets affected by tissue pH and RIN were identified. Moreover, we examined the functions of these genes by enrichment analysis and upstream regulator analysis.ResultsWe identified 2,043 genes (24.7%) whose expressions were highly correlated with pH; 3,004 genes (36.3%) whose expressions were highly correlated with RIN; and 1,293 genes (15.6%) whose expressions were highly correlated with both pH and RIN. Genes commonly affected by tissue pH and RIN were highly associated with energy production and the immune system. In addition, genes uniquely affected by tissue pH were highly associated with the cell cycle, whereas those uniquely affected by RIN were highly associated with RNA processing.ConclusionThe current study elucidated the influence of pH and RIN on gene expression profiling and identified gene sets whose expressions were affected by tissue pH or RIN. These findings would be helpful in the control of confounders for future postmortem brain studies.
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spelling doaj.art-957c8a4e574a4db4afe10681d1ff595e2023-07-15T03:10:08ZengFrontiers Media S.A.Frontiers in Psychiatry1664-06402023-07-011410.3389/fpsyt.2023.11565241156524The influence of tissue pH and RNA integrity number on gene expression of human postmortem brainKazusa Miyahara0Mizuki Hino1Mizuki Hino2Zhiqian Yu3Chiaki Ono4Atsuko Nagaoka5Masataka Hatano6Risa Shishido7Hirooki Yabe8Hiroaki Tomita9Hiroaki Tomita10Yasuto Kunii11Yasuto Kunii12Department of Disaster Psychiatry, International Research Institute of Disaster Science, Tohoku University, Sendai, JapanDepartment of Disaster Psychiatry, International Research Institute of Disaster Science, Tohoku University, Sendai, JapanDepartment of Neuropsychiatry, School of Medicine, Fukushima Medical University, Fukushima, JapanDepartment of Psychiatry, Graduate School of Medicine, Tohoku University, Sendai, Miyagi, JapanDepartment of Psychiatry, Graduate School of Medicine, Tohoku University, Sendai, Miyagi, JapanDepartment of Neuropsychiatry, School of Medicine, Fukushima Medical University, Fukushima, JapanDepartment of Neuropsychiatry, School of Medicine, Fukushima Medical University, Fukushima, JapanDepartment of Neuropsychiatry, School of Medicine, Fukushima Medical University, Fukushima, JapanDepartment of Neuropsychiatry, School of Medicine, Fukushima Medical University, Fukushima, JapanDepartment of Psychiatry, Graduate School of Medicine, Tohoku University, Sendai, Miyagi, JapanDepartment of Psychiatry, Tohoku University Hospital, Sendai, Miyagi, JapanDepartment of Disaster Psychiatry, International Research Institute of Disaster Science, Tohoku University, Sendai, JapanDepartment of Neuropsychiatry, School of Medicine, Fukushima Medical University, Fukushima, JapanBackgroundEvaluating and controlling confounders are necessary when investigating molecular pathogenesis using human postmortem brain tissue. Particularly, tissue pH and RNA integrity number (RIN) are valuable indicators for controlling confounders. However, the influences of these indicators on the expression of each gene in postmortem brain have not been fully investigated. Therefore, we aimed to assess these effects on gene expressions of human brain samples.MethodsWe isolated total RNA from occipital lobes of 13 patients with schizophrenia and measured the RIN and tissue pH. Gene expression was analyzed and gene sets affected by tissue pH and RIN were identified. Moreover, we examined the functions of these genes by enrichment analysis and upstream regulator analysis.ResultsWe identified 2,043 genes (24.7%) whose expressions were highly correlated with pH; 3,004 genes (36.3%) whose expressions were highly correlated with RIN; and 1,293 genes (15.6%) whose expressions were highly correlated with both pH and RIN. Genes commonly affected by tissue pH and RIN were highly associated with energy production and the immune system. In addition, genes uniquely affected by tissue pH were highly associated with the cell cycle, whereas those uniquely affected by RIN were highly associated with RNA processing.ConclusionThe current study elucidated the influence of pH and RIN on gene expression profiling and identified gene sets whose expressions were affected by tissue pH or RIN. These findings would be helpful in the control of confounders for future postmortem brain studies.https://www.frontiersin.org/articles/10.3389/fpsyt.2023.1156524/fullschizophreniapostmortem brainmicroarraypHRNA integrity number
spellingShingle Kazusa Miyahara
Mizuki Hino
Mizuki Hino
Zhiqian Yu
Chiaki Ono
Atsuko Nagaoka
Masataka Hatano
Risa Shishido
Hirooki Yabe
Hiroaki Tomita
Hiroaki Tomita
Yasuto Kunii
Yasuto Kunii
The influence of tissue pH and RNA integrity number on gene expression of human postmortem brain
Frontiers in Psychiatry
schizophrenia
postmortem brain
microarray
pH
RNA integrity number
title The influence of tissue pH and RNA integrity number on gene expression of human postmortem brain
title_full The influence of tissue pH and RNA integrity number on gene expression of human postmortem brain
title_fullStr The influence of tissue pH and RNA integrity number on gene expression of human postmortem brain
title_full_unstemmed The influence of tissue pH and RNA integrity number on gene expression of human postmortem brain
title_short The influence of tissue pH and RNA integrity number on gene expression of human postmortem brain
title_sort influence of tissue ph and rna integrity number on gene expression of human postmortem brain
topic schizophrenia
postmortem brain
microarray
pH
RNA integrity number
url https://www.frontiersin.org/articles/10.3389/fpsyt.2023.1156524/full
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