Involvement of the nuclear factor-κB transcriptional complex in prefrontal cortex immune activation in bipolar disorder
Abstract Bipolar disorder and schizophrenia have multiple clinical and genetic features in common, including shared risk associated with overlapping susceptibility loci in immune-related genes. Higher activity of the nuclear factor-κB (NF-κB) transcription factor complex, which regulates the transcr...
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2021-01-01
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Series: | Translational Psychiatry |
Online Access: | https://doi.org/10.1038/s41398-020-01092-x |
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doaj-5ad8ef912fff4b12b81d1ed0960cb4232021-01-17T12:57:28ZengNature Publishing GroupTranslational Psychiatry2158-31882021-01-0111111010.1038/s41398-020-01092-xInvolvement of the nuclear factor-κB transcriptional complex in prefrontal cortex immune activation in bipolar disorderKaitlyn M. Roman0Aaron K. Jenkins1David A. Lewis2David W. Volk3Department of Psychiatry, University of PittsburghDepartment of Psychiatry, University of PittsburghDepartment of Psychiatry, University of PittsburghDepartment of Psychiatry, University of PittsburghAbstract Bipolar disorder and schizophrenia have multiple clinical and genetic features in common, including shared risk associated with overlapping susceptibility loci in immune-related genes. Higher activity of the nuclear factor-κB (NF-κB) transcription factor complex, which regulates the transcription of multiple immune markers, has been reported to contribute to immune activation in the prefrontal cortex in schizophrenia. These findings suggest the hypothesis that elevated NF-κB activity is present in the prefrontal cortex in bipolar disorder in a manner similar to that seen in schizophrenia. Therefore, we quantified levels of NF-κB-related mRNAs in the prefrontal cortex of 35 matched pairs of bipolar disorder and unaffected comparison subjects using quantitative PCR. We found that transcript levels were higher in the prefrontal cortex of bipolar disorder subjects for several NF-κB family members, NF-κB activation receptors, and NF-κB-regulated mRNAs, and were lower for an NF-κB inhibitor. Transcript levels for NF-κB family members, NF-κB activation receptors, and NF-κB-regulated mRNAs levels were also highly correlated with each other. This pattern of elevated transcript levels for NF-κB-related markers in bipolar disorder is similar to that previously reported in schizophrenia, suggesting that cortical immune activation is a shared pathophysiological feature between the two disorders.https://doi.org/10.1038/s41398-020-01092-x |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Kaitlyn M. Roman Aaron K. Jenkins David A. Lewis David W. Volk |
spellingShingle |
Kaitlyn M. Roman Aaron K. Jenkins David A. Lewis David W. Volk Involvement of the nuclear factor-κB transcriptional complex in prefrontal cortex immune activation in bipolar disorder Translational Psychiatry |
author_facet |
Kaitlyn M. Roman Aaron K. Jenkins David A. Lewis David W. Volk |
author_sort |
Kaitlyn M. Roman |
title |
Involvement of the nuclear factor-κB transcriptional complex in prefrontal cortex immune activation in bipolar disorder |
title_short |
Involvement of the nuclear factor-κB transcriptional complex in prefrontal cortex immune activation in bipolar disorder |
title_full |
Involvement of the nuclear factor-κB transcriptional complex in prefrontal cortex immune activation in bipolar disorder |
title_fullStr |
Involvement of the nuclear factor-κB transcriptional complex in prefrontal cortex immune activation in bipolar disorder |
title_full_unstemmed |
Involvement of the nuclear factor-κB transcriptional complex in prefrontal cortex immune activation in bipolar disorder |
title_sort |
involvement of the nuclear factor-κb transcriptional complex in prefrontal cortex immune activation in bipolar disorder |
publisher |
Nature Publishing Group |
series |
Translational Psychiatry |
issn |
2158-3188 |
publishDate |
2021-01-01 |
description |
Abstract Bipolar disorder and schizophrenia have multiple clinical and genetic features in common, including shared risk associated with overlapping susceptibility loci in immune-related genes. Higher activity of the nuclear factor-κB (NF-κB) transcription factor complex, which regulates the transcription of multiple immune markers, has been reported to contribute to immune activation in the prefrontal cortex in schizophrenia. These findings suggest the hypothesis that elevated NF-κB activity is present in the prefrontal cortex in bipolar disorder in a manner similar to that seen in schizophrenia. Therefore, we quantified levels of NF-κB-related mRNAs in the prefrontal cortex of 35 matched pairs of bipolar disorder and unaffected comparison subjects using quantitative PCR. We found that transcript levels were higher in the prefrontal cortex of bipolar disorder subjects for several NF-κB family members, NF-κB activation receptors, and NF-κB-regulated mRNAs, and were lower for an NF-κB inhibitor. Transcript levels for NF-κB family members, NF-κB activation receptors, and NF-κB-regulated mRNAs levels were also highly correlated with each other. This pattern of elevated transcript levels for NF-κB-related markers in bipolar disorder is similar to that previously reported in schizophrenia, suggesting that cortical immune activation is a shared pathophysiological feature between the two disorders. |
url |
https://doi.org/10.1038/s41398-020-01092-x |
work_keys_str_mv |
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