Epub – Biological Psychiatry
The Role of the Nuclear Factor-κB Transcriptional Complex in Cortical Immune Activation in Schizophrenia
Volk DW, Moroco AE, Roman KM, Edelson JR, Lewis DA
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.
Volk DW, Moroco AE, Roman KM, Edelson JR, Lewis DA. The Role of the Nuclear Factor-κB Transcriptional Complex in Cortical Immune Activation in Schizophrenia. Biol Psychiatry. 2018 Jun 28. pii: S0006-3223(18)31629-9. doi: 10.1016/j.biopsych.2018.06.015. [Epub ahead of print]. PubMed PMID: 30082065.
Laboratory of David A. Lewis, MD
Researching the neural circuitry of the prefrontal cortex and related brain regions, and the alterations of this circuitry in schizophrenia.
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