Dataset Information

The Role of the Nuclear Factor-κB Transcriptional Complex in Cortical Immune Activation in Schizophrenia.

ABSTRACT:

Background

Transcript levels for cytokines and the viral restriction factor interferon-induced transmembrane protein are markedly higher in the prefrontal cortex in schizophrenia. These gene products are regulated by the nuclear factor-κB (NF-κB) transcriptional complex. NF-κB activity, which requires the formation of NF-κB family member heterodimers, is regulated by activation receptors, kinases, and inhibitors. Whether any of these factors are altered in schizophrenia is not known. It is also unclear whether NF-κB-related disturbances reflect ongoing cortical immune activation or a long-lasting response to a prenatal immune-related insult.

Methods

Transcript levels for NF-κB pathway markers were assessed using quantitative polymerase chain reaction in the prefrontal cortex from 1) 62 matched pairs of schizophrenia and unaffected comparison subjects, 2) antipsychotic-exposed monkeys, and 3) adult mice exposed prenatally to maternal immune activation or in adulthood to the immune stimulant polyinosinic-polycytidylic acid.

Results

In schizophrenia subjects, but not antipsychotic-exposed monkeys, we found higher messenger RNA levels for 1) most NF-κB family members, 2) all NF-κB activation receptors, 3) several kinases, and 4) one inhibitor (IκBα) whose transcript level is itself regulated by NF-κB activity. A similar pattern of elevated NF-κB-related messenger RNA levels was seen in adult mice that received daily polyinosinic-polycytidylic acid injections, but not in adult mice subjected to maternal immune activation in utero.

Conclusions

Higher NF-κB activity, evidenced by elevated transcript levels for NF-κB family members, activation receptors, and kinases, may contribute to increased markers of cortical immune activation in schizophrenia.

SUBMITTER: Volk DW

PROVIDER: S-EPMC6289758 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Publications

The Role of the Nuclear Factor-κB Transcriptional Complex in Cortical Immune Activation in Schizophrenia.

Volk David W DW Moroco Annie E AE Roman Kaitlyn M KM Edelson Jessica R JR Lewis David A DA

Biological psychiatry 20180628 1

<h4>Background</h4>Transcript levels for cytokines and the viral restriction factor interferon-induced transmembrane protein are markedly higher in the prefrontal cortex in schizophrenia. These gene products are regulated by the nuclear factor-κB (NF-κB) transcriptional complex. NF-κB activity, which requires the formation of NF-κB family member heterodimers, is regulated by activation receptors, kinases, and inhibitors. Whether any of these factors are altered in schizophrenia is not known. It ...[more]

PMID: 30082065

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Dataset Information

The Role of the Nuclear Factor-κB Transcriptional Complex in Cortical Immune Activation in Schizophrenia.

Background

Methods

Results

Conclusions

Publications

The Role of the Nuclear Factor-κB Transcriptional Complex in Cortical Immune Activation in Schizophrenia.

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