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Detailed Postmortem Profiling of Inflammatory Mediators Expression Revealed Post-inflammatory Alternation in the Superior Temporal Gyrus of Schizophrenia

Recent studies have lent support to the possibility that inflammation is associated with the pathology of schizophrenia. In the study of measurement of inflammatory mediators, which are markers of inflammation, elevated inflammatory cytokine levels in the brain and blood have been reported in patien...

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Autores principales: Izumi, Ryuta, Hino, Mizuki, Wada, Akira, Nagaoka, Atsuko, Kawamura, Takashi, Mori, Tsutomu, Sainouchi, Makoto, Kakita, Akiyoshi, Kasai, Kiyoto, Kunii, Yasuto, Yabe, Hirooki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012534/
https://www.ncbi.nlm.nih.gov/pubmed/33815179
http://dx.doi.org/10.3389/fpsyt.2021.653821
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author Izumi, Ryuta
Hino, Mizuki
Wada, Akira
Nagaoka, Atsuko
Kawamura, Takashi
Mori, Tsutomu
Sainouchi, Makoto
Kakita, Akiyoshi
Kasai, Kiyoto
Kunii, Yasuto
Yabe, Hirooki
author_facet Izumi, Ryuta
Hino, Mizuki
Wada, Akira
Nagaoka, Atsuko
Kawamura, Takashi
Mori, Tsutomu
Sainouchi, Makoto
Kakita, Akiyoshi
Kasai, Kiyoto
Kunii, Yasuto
Yabe, Hirooki
author_sort Izumi, Ryuta
collection PubMed
description Recent studies have lent support to the possibility that inflammation is associated with the pathology of schizophrenia. In the study of measurement of inflammatory mediators, which are markers of inflammation, elevated inflammatory cytokine levels in the brain and blood have been reported in patients with schizophrenia. Several postmortem brain studies have also reported changes in the expression of inflammatory cytokines. However, it is not clear how these elevated inflammatory cytokines interact with other inflammatory mediators, and their association with the pathology of schizophrenia. We comprehensively investigated the expression of 30 inflammatory mediators in the superior temporal gyrus (STG) of 24 patients with schizophrenia and 26 controls using a multiplex method. Overall, inflammatory mediator expression in the STG was mostly unchanged. However, the expression of interleukin (IL)1-α and interferon-gamma-inducible protein (IP)-10 was decreased [IL-1α, median (IQR), 0.51 (0.37–0.70) vs. 0.87 (0.47–1.23), p = 0.01; IP-10, 13.99 (8.00–36.64) vs. 30.29 (10.23–134.73), p = 0.05], whereas that of IFN-α was increased [2.34 (1.84–4.48) vs. 1.94 (1.39–2.36), p = 0.04] in schizophrenia, although these alterations did not remain significant after multiple testing. Clustering based on inflammatory mediator expression pattern and analysis of upstream transcription factors using pathway analysis revealed that the suppression of IL-1α and IP-10 protein expression may be induced by regulation of a common upstream pathway. Neuroinflammation is important in understanding the biology of schizophrenia. While neuroimaging has been previously used, direct observation to determine the expression of inflammatory mediators is necessary. In this study, we identified protein changes, previously unreported, using comprehensive protein analysis in STG. These results provide insight into post-inflammatory alternation in chronic schizophrenia.
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spelling pubmed-80125342021-04-02 Detailed Postmortem Profiling of Inflammatory Mediators Expression Revealed Post-inflammatory Alternation in the Superior Temporal Gyrus of Schizophrenia Izumi, Ryuta Hino, Mizuki Wada, Akira Nagaoka, Atsuko Kawamura, Takashi Mori, Tsutomu Sainouchi, Makoto Kakita, Akiyoshi Kasai, Kiyoto Kunii, Yasuto Yabe, Hirooki Front Psychiatry Psychiatry Recent studies have lent support to the possibility that inflammation is associated with the pathology of schizophrenia. In the study of measurement of inflammatory mediators, which are markers of inflammation, elevated inflammatory cytokine levels in the brain and blood have been reported in patients with schizophrenia. Several postmortem brain studies have also reported changes in the expression of inflammatory cytokines. However, it is not clear how these elevated inflammatory cytokines interact with other inflammatory mediators, and their association with the pathology of schizophrenia. We comprehensively investigated the expression of 30 inflammatory mediators in the superior temporal gyrus (STG) of 24 patients with schizophrenia and 26 controls using a multiplex method. Overall, inflammatory mediator expression in the STG was mostly unchanged. However, the expression of interleukin (IL)1-α and interferon-gamma-inducible protein (IP)-10 was decreased [IL-1α, median (IQR), 0.51 (0.37–0.70) vs. 0.87 (0.47–1.23), p = 0.01; IP-10, 13.99 (8.00–36.64) vs. 30.29 (10.23–134.73), p = 0.05], whereas that of IFN-α was increased [2.34 (1.84–4.48) vs. 1.94 (1.39–2.36), p = 0.04] in schizophrenia, although these alterations did not remain significant after multiple testing. Clustering based on inflammatory mediator expression pattern and analysis of upstream transcription factors using pathway analysis revealed that the suppression of IL-1α and IP-10 protein expression may be induced by regulation of a common upstream pathway. Neuroinflammation is important in understanding the biology of schizophrenia. While neuroimaging has been previously used, direct observation to determine the expression of inflammatory mediators is necessary. In this study, we identified protein changes, previously unreported, using comprehensive protein analysis in STG. These results provide insight into post-inflammatory alternation in chronic schizophrenia. Frontiers Media S.A. 2021-03-18 /pmc/articles/PMC8012534/ /pubmed/33815179 http://dx.doi.org/10.3389/fpsyt.2021.653821 Text en Copyright © 2021 Izumi, Hino, Wada, Nagaoka, Kawamura, Mori, Sainouchi, Kakita, Kasai, Kunii and Yabe. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Psychiatry
Izumi, Ryuta
Hino, Mizuki
Wada, Akira
Nagaoka, Atsuko
Kawamura, Takashi
Mori, Tsutomu
Sainouchi, Makoto
Kakita, Akiyoshi
Kasai, Kiyoto
Kunii, Yasuto
Yabe, Hirooki
Detailed Postmortem Profiling of Inflammatory Mediators Expression Revealed Post-inflammatory Alternation in the Superior Temporal Gyrus of Schizophrenia
title Detailed Postmortem Profiling of Inflammatory Mediators Expression Revealed Post-inflammatory Alternation in the Superior Temporal Gyrus of Schizophrenia
title_full Detailed Postmortem Profiling of Inflammatory Mediators Expression Revealed Post-inflammatory Alternation in the Superior Temporal Gyrus of Schizophrenia
title_fullStr Detailed Postmortem Profiling of Inflammatory Mediators Expression Revealed Post-inflammatory Alternation in the Superior Temporal Gyrus of Schizophrenia
title_full_unstemmed Detailed Postmortem Profiling of Inflammatory Mediators Expression Revealed Post-inflammatory Alternation in the Superior Temporal Gyrus of Schizophrenia
title_short Detailed Postmortem Profiling of Inflammatory Mediators Expression Revealed Post-inflammatory Alternation in the Superior Temporal Gyrus of Schizophrenia
title_sort detailed postmortem profiling of inflammatory mediators expression revealed post-inflammatory alternation in the superior temporal gyrus of schizophrenia
topic Psychiatry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012534/
https://www.ncbi.nlm.nih.gov/pubmed/33815179
http://dx.doi.org/10.3389/fpsyt.2021.653821
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