Analysis of networks in the dorsolateral prefrontal cortex in chronic schizophrenia: Relevance of altered immune response
Por:
Vera-Montecinos A, Rodríguez-Mias R, Vila E, Villén J and Ramos B
Publicada:
23 mar 2023
Ahead of Print:
23 mar 2023
Resumen:
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.
Filiaciones:
:
Psiquiatria Molecular, Parc Sanitari Sant Joan de Déu, Institut de Recerca Sant Joan de Déu, Sant Boi de Llobregat, Spain
Rodríguez-Mias R:
Department of Genome Sciences, School of Medicine, University of Washington, Seattle, WA, United States
Vila E:
Psiquiatria Molecular, Parc Sanitari Sant Joan de Déu, Institut de Recerca Sant Joan de Déu, Sant Boi de Llobregat, Spain
Villén J:
Department of Genome Sciences, School of Medicine, University of Washington, Seattle, WA, United States
Ramos B:
Psiquiatria Molecular, Parc Sanitari Sant Joan de Déu, Institut de Recerca Sant Joan de Déu, Sant Boi de Llobregat, Spain
Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM (Biomedical Network Research Center of Mental Health), Ministry of Economy, Industry and Competitiveness, Institute of Health Carlos III, Madrid, Spain
Department de Bioquímica i Biología Molecular, Facultat de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain
Facultat de Medicina, Universitat de Vic-Universitat Central de Catalunya, Vic, Spain
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