| Abstract |
An increase in apoptotic events may underlie neuropathology in精神分裂症. By data-mining approaches, we identified significant expression changes in death receptor signaling pathways in the dorsolateral prefrontal cortex (DLPFC) of patients with精神分裂症, particularly implicating the Tumor Necrosis Factor Superfamily member 6 (FAS) receptor and the Tumor Necrosis Factor [ligand] Superfamily member 13 (TNFSF13) in精神分裂症. We sought to confirm and replicate in an independent tissue collection the noted mRNA changes with quantitative real-time RT-PCR. To test for regional and diagnostic specificity, tissue from orbital frontal cortex (OFC) was examined and a bipolar disorder group included. In精神分裂症, we confirmed and replicated significantly increased expression ofTNFSF13mRNA in the DLPFC. Also, a significantly larger proportion of subjects in the精神分裂症group had elevated FAS receptor expression in the DLPFC relative to unaffected controls. These changes were not observed in the bipolar disorder group. In the OFC, there were no significant differences inTNFSF13or FAS receptor mRNA expression. Decreases in BH3 interacting domain death agonist (BID) mRNA transcript levels were found in the精神分裂症and bipolar disorder groups affecting both the DLPFC and the OFC. We tested ifTNFSF13mRNA expression correlated with neuronal mRNAs in the DLPFC, and found significant negative correlations with interneuron markers, parvalbumin and somatostatin, and a positive correlation with PPP1R9B (spinophilin), but not DLG4 (PSD-95). The expression ofTNFSF13mRNA in DLPFC correlated negatively with tissue pH, but decreasing pH in cultured cells did not cause increasedTNFSF13mRNA nor did exogenousTNFSF13decrease pH. We concluded that increasedTNFSF13expression may be one of several cell-death cytokine abnormalities that contribute to the observed brain pathology in精神分裂症, and while increasedTNFSF13may be associated with lower brain pH, the change is not necessarily causally related to brain pH. |