Analysis of Molecular Networks in the Cerebellum in Chronic Schizophrenia: Modulation by Early Postnatal Life Stressors in Murine Models.
Por:
Vera-Montecinos A, Rodríguez-Mias R, MacDowell KS, García-Bueno B, Bris ÁG, Caso JR, Villén J and Ramos B
Publicada:
17 sep 2021
Ahead of Print:
17 sep 2021
Resumen:
Despite the growing importance of the cerebellum as a region highly vulnerable to accumulating molecular errors in schizophrenia, limited information is available regarding altered molecular networks with potential therapeutic targets. To identify altered networks, we conducted one-shot liquid chromatography-tandem mass spectrometry in postmortem cerebellar cortex in schizophrenia and healthy individuals followed by bioinformatic analysis (PXD024937 identifier in ProteomeXchange repository). A total of 108 up-regulated proteins were enriched in stress-related proteins, half of which were also enriched in axonal cytoskeletal organization and vesicle-mediated transport. A total of 142 down-regulated proteins showed an enrichment in proteins involved in mitochondrial disease, most of which were also enriched in energy-related biological functions. Network analysis identified a mixed module of mainly axonal-related pathways for up-regulated proteins with a high number of interactions for stress-related proteins. Energy metabolism and neutrophil degranulation modules were found for down-regulated proteins. Further, two double-hit postnatal stress murine models based on maternal deprivation combined with social isolation or chronic restraint stress were used to investigate the most robust candidates of generated networks. CLASP1 from the axonal module in the model of maternal deprivation was combined with social isolation, while YWHAZ was not altered in either model. METTL7A from the degranulation pathway was reduced in both models and was identified as altered also in previous gene expression studies, while NDUFB9 from the energy network was reduced only in the model of maternal deprivation combined with social isolation. This work provides altered stress- and mitochondrial disease-related proteins involved in energy, immune and axonal networks in the cerebellum in schizophrenia as possible novel targets for therapeutic interventions and suggests that METTL7A is a possible relevant altered stress-related protein in this context.
Filiaciones:
Vera-Montecinos A:
Psiquiatria Molecular, Institut de Recerca Sant Joan de Déu, Santa Rosa 39-57, 08950 Esplugues de Llobregat, Spain
Rodríguez-Mias R:
Department of Genome Sciences, School of Medicine, University of Washington, 3720 15th Ave NE, Seattle, WA 98195, USA
MacDowell KS:
Departamento de Farmacología y Toxicología, Facultad de Medicina, Universidad Complutense de Madrid, Instituto de Investigación Sanitaria Hospital 12 de Octubre (Imas12), Instituto Universitario de Investigación en Neuroquímica IUIN-UCM, Avda. Complutense s/n, 28040 Madrid, Spain
Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM (Biomedical Network Research Center of Mental Health), Institute of Health Carlos III, 28029 Madrid, Spain
García-Bueno B:
Departamento de Farmacología y Toxicología, Facultad de Medicina, Universidad Complutense de Madrid, Instituto de Investigación Sanitaria Hospital 12 de Octubre (Imas12), Instituto Universitario de Investigación en Neuroquímica IUIN-UCM, Avda. Complutense s/n, 28040 Madrid, Spain
Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM (Biomedical Network Research Center of Mental Health), Institute of Health Carlos III, 28029 Madrid, Spain
Bris ÁG:
Departamento de Farmacología y Toxicología, Facultad de Medicina, Universidad Complutense de Madrid, Instituto de Investigación Sanitaria Hospital 12 de Octubre (Imas12), Instituto Universitario de Investigación en Neuroquímica IUIN-UCM, Avda. Complutense s/n, 28040 Madrid, Spain
Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM (Biomedical Network Research Center of Mental Health), Institute of Health Carlos III, 28029 Madrid, Spain
Caso JR:
Departamento de Farmacología y Toxicología, Facultad de Medicina, Universidad Complutense de Madrid, Instituto de Investigación Sanitaria Hospital 12 de Octubre (Imas12), Instituto Universitario de Investigación en Neuroquímica IUIN-UCM, Avda. Complutense s/n, 28040 Madrid, Spain
Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM (Biomedical Network Research Center of Mental Health), Institute of Health Carlos III, 28029 Madrid, Spain
Villén J:
Department of Genome Sciences, School of Medicine, University of Washington, 3720 15th Ave NE, Seattle, WA 98195, USA
Ramos B:
Psiquiatria Molecular, Institut de Recerca Sant Joan de Déu, Santa Rosa 39-57, 08950 Esplugues de Llobregat, Spain
Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM (Biomedical Network Research Center of Mental Health), Institute of Health Carlos III, 28029 Madrid, Spain
Parc Sanitari Sant Joan de Déu, Doctor Antoni Pujadas 42, 08830 Sant Boi de Llobregat, Spain
Faculty of Medicine, University of Vic-Central University of Catalonia, 08500 Vic, Spain
Departamento de Bioquímica i Biología Molecular, Facultat de Medicina, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain
Open Access
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