TY - JOUR
T1 - Detailed Postmortem Profiling of Inflammatory Mediators Expression Revealed Post-inflammatory Alternation in the Superior Temporal Gyrus of Schizophrenia
AU - Izumi, Ryuta
AU - Hino, Mizuki
AU - Wada, Akira
AU - Nagaoka, Atsuko
AU - Kawamura, Takashi
AU - Mori, Tsutomu
AU - Sainouchi, Makoto
AU - Kakita, Akiyoshi
AU - Kasai, Kiyoto
AU - Kunii, Yasuto
AU - Yabe, Hirooki
N1 - Funding Information:
This work was supported in part by Grant-in-Aid for Young Scientists(B) from Japan Society for the Promotion of Science (Grant No. 16K19752); the Strategic Research Program for Brain Sciences from AMED (Grant Nos. JP20dm0107161, 20dm0207074h0001, JP20dm0107104, and JP20dm0107107) and Grant-in-Aid for Scientific Research on Innovative Areas from the MEXT (Grant Nos. JP16H06277 and JP19H05223). In addition, this study was supported by the Collaborative Research Project of Brain Research Institute, Niigata University (Grant No. 201917).
Publisher Copyright:
© Copyright © 2021 Izumi, Hino, Wada, Nagaoka, Kawamura, Mori, Sainouchi, Kakita, Kasai, Kunii and Yabe.
PY - 2021/3/18
Y1 - 2021/3/18
N2 - 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.
AB - 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.
KW - IL1A (IL1α)
KW - IP10
KW - inflammatory meadators
KW - postmortem
KW - schizophrenia
KW - superior-temporal gyrus
UR - http://www.scopus.com/inward/record.url?scp=85103488478&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85103488478&partnerID=8YFLogxK
U2 - 10.3389/fpsyt.2021.653821
DO - 10.3389/fpsyt.2021.653821
M3 - Article
AN - SCOPUS:85103488478
SN - 1664-0640
VL - 12
JO - Frontiers in Psychiatry
JF - Frontiers in Psychiatry
M1 - 653821
ER -
