Table4_Analysis of networks in the dorsolateral prefrontal cortex in chronic schizophrenia: Relevance of altered immune response.XLSX

The dorsolateral prefrontal cortex (DLPFC) has a crucial role in cognitive functioning and negative symptoms in schizophrenia. However, limited information of altered protein networks is available in this region in schizophrenia. We performed a proteomic analysis using single-shot liquid chromatography-tandem mass spectrometry of grey matter of postmortem DLPFC in chronic schizophrenia subjects (n = 20) and unaffected subjects (n = 20) followed by bioinformatic analysis to identify altered protein networks in schizophrenia (PXD024939 identifier in ProteomeXchange repository). Our results displayed a proteome profile in the DLPFC of 1989 proteins. 43 proteins were found significantly altered in schizophrenia. Analysis of this panel showed an enrichment of biological processes implicated in vesicle-mediated transport, processing and antigen presentation via MHC class II, intracellular transport and selenium metabolism. The enriched identified pathways were MHC class II antigen presentation, vesicle-mediated transport, Golgi ER retrograde transport, Nef mediated CD8 downregulation and the immune system. All these enriched categories were found to be downregulated. Furthermore, our network analyses showed crosstalk between proteins involved in MHC class II antigen presentation, membrane trafficking, Golgi-to-ER retrograde transport, Nef-mediated CD8 downregulation and the immune system with only one module built by 13 proteins. RAB7A showed eight interactions with proteins of all these pathways. Our results provide an altered molecular network involved in immune response in the DLPFC in schizophrenia with a central role of RAB7A. These results suggest that RAB7A or other proteins of this network could be potential targets for novel pharmacological strategies in schizophrenia for improving cognitive and negative symptoms.

额叶皮层背外侧区（DLPFC）在认知功能以及精神分裂症的阴性症状中扮演着至关重要的角色。然而，关于该区域蛋白质网络改变的信息在精神分裂症中相对有限。本研究通过对慢性精神分裂症病例（n = 20）和未受影响对照者（n = 20）的尸检DLPFC灰质进行单次液相色谱串联质谱分析，随后进行生物信息学分析，以识别精神分裂症中的改变蛋白质网络（ProteomeXchange仓库中的PXD024939标识符）。我们的结果显示，在DLPFC中存在1989种蛋白质的蛋白质组特征。在精神分裂症患者中，发现了43种蛋白质发生显著改变。对这些蛋白质组的分析揭示了与囊泡介导的运输、处理以及通过MHC II类分子进行抗原呈递、细胞内运输和硒代谢相关的生物学过程的富集。富集的识别途径包括MHC II类抗原呈递、囊泡介导的运输、高尔基体-内质网逆向运输、Nef介导的CD8下调以及免疫系统。所有这些富集的类别均被发现下调。此外，我们的网络分析显示，MHC II类抗原呈递、膜转运、高尔基体至内质网逆向运输、Nef介导的CD8下调和免疫系统中的蛋白质存在相互作用，并且仅由13种蛋白质构建的单个模块。RAB7A与这些途径中的所有蛋白质表现出八种相互作用。我们的研究结果提供了涉及精神分裂症DLPFC中免疫反应的改变分子网络，其中RAB7A发挥着核心作用。这些结果提示，RAB7A或该网络中的其他蛋白质可能是精神分裂症中新型药理策略的潜在靶点，以改善认知和阴性症状。