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Different changes in cortical tumor necrosis factor-α-related pathways in schizophrenia and mood disorders

Abstract

The growing body of evidence implicating tumor necrosis factor-α (TNFα) in the pathophysiology of psychiatric disorders led us to measure levels of that protein in the cortex of subjects with major depressive disorders (MDD). Having reported an increase (458%) in the levels of the transmembrane (tmTNFα), but not the soluble (sTNFα), form of the protein in Brodmann's area (BA) 46, but not 24, in people with the disorder, we decided to examine additional components of TNFα-related pathways in the same regions in people with MDD and extend our studies to the same cortical regions of people with schizophrenia (Sz) and bipolar disorders (BD). Using postmortem tissue, western blots and quantitative PCR, we have now shown there is a significant increase (305%) in tmTNFα in Brodmann's area 24, but not 46, from subjects with BD, and that levels of the protein were not altered in Sz. Levels of sTNFα were not altered in BD or Sz. In addition, we have shown that levels of TNF receptor 1 (TNFR1) mRNA are increased in BA 24 (53%) and BA 46 (82%) in people with Sz, whereas levels of TNFR2 mRNA was decreased in BA 46 in people with mood disorders (MDD=−51%; BD=−67%). Levels of proteins frequently used as surrogate markers of neuronal, astrocytic and microglia numbers, as well as levels of the pro-inflammatory marker (interleukin 1β), were not changed in the cortex of people with mood disorders. Our data suggest there are differential changes in TNFα-related markers in the cortex of people with MDD, BD and Sz that may not be related to classical inflammation and may cause changes in different TNFα-related signaling pathways.

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Acknowledgements

BD is an NHMRC Senior Research Fellow and ES is an ARC Future Fellow. This work was supported in part by grants-in-aid from the Rebecca Cooper Medical Research Foundation and the Victorian Government's Operational Infrastructure Support program. Financial support for the experiments described in this paper was from the National Health and Medical Research Council, Australian Research Council, The State Government of Victoria (infrastructure) and The Rebecca L Cooper Medical Research Foundation.

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Dean, B., Gibbons, A., Tawadros, N. et al. Different changes in cortical tumor necrosis factor-α-related pathways in schizophrenia and mood disorders. Mol Psychiatry 18, 767–773 (2013). https://doi.org/10.1038/mp.2012.95

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