{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T12:29:14Z","timestamp":1787228954144,"version":"build-2736575974"},"reference-count":81,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2021,9,17]],"date-time":"2021-09-17T00:00:00Z","timestamp":1631836800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Miguel Servet","award":["MS16\/00153-CP16\/00153"],"award-info":[{"award-number":["MS16\/00153-CP16\/00153"]}]},{"name":"CONICYT-Becas Chile 2015","award":["72160426"],"award-info":[{"award-number":["72160426"]}]},{"DOI":"10.13039\/501100010198","name":"Ministerio de Econom\u00eda, Industria y Competitividad, Gobierno de Espa\u00f1a","doi-asserted-by":"publisher","award":["SAF2016-75500R"],"award-info":[{"award-number":["SAF2016-75500R"]}],"id":[{"id":"10.13039\/501100010198","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["GM 119536 and R01 NS098329"],"award-info":[{"award-number":["GM 119536 and R01 NS098329"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\u2013tandem 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.<\/jats:p>","DOI":"10.3390\/ijms221810076","type":"journal-article","created":{"date-parts":[[2021,9,17]],"date-time":"2021-09-17T21:23:29Z","timestamp":1631913809000},"page":"10076","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Analysis of Molecular Networks in the Cerebellum in Chronic Schizophrenia: Modulation by Early Postnatal Life Stressors in Murine Models"],"prefix":"10.3390","volume":"22","author":[{"given":"Am\u00e9rica","family":"Vera-Montecinos","sequence":"first","affiliation":[{"name":"Psiquiatria Molecular, Institut de Recerca Sant Joan de D\u00e9u, Santa Rosa 39\u201357, 08950 Esplugues de Llobregat, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricard","family":"Rodr\u00edguez-Mias","sequence":"additional","affiliation":[{"name":"Department of Genome Sciences, School of Medicine, University of Washington, 3720 15th Ave NE, Seattle, WA 98195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1527-8895","authenticated-orcid":false,"given":"Karina S.","family":"MacDowell","sequence":"additional","affiliation":[{"name":"Departamento de Farmacolog\u00eda y Toxicolog\u00eda, Facultad de Medicina, Universidad Complutense de Madrid, Instituto de Investigaci\u00f3n Sanitaria Hospital 12 de Octubre (Imas12), Instituto Universitario de Investigaci\u00f3n en Neuroqu\u00edmica IUIN-UCM, Avda. Complutense s\/n, 28040 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Salud Mental, CIBERSAM (Biomedical Network Research Center of Mental Health), Institute of Health Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Borja","family":"Garc\u00eda-Bueno","sequence":"additional","affiliation":[{"name":"Departamento de Farmacolog\u00eda y Toxicolog\u00eda, Facultad de Medicina, Universidad Complutense de Madrid, Instituto de Investigaci\u00f3n Sanitaria Hospital 12 de Octubre (Imas12), Instituto Universitario de Investigaci\u00f3n en Neuroqu\u00edmica IUIN-UCM, Avda. Complutense s\/n, 28040 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Salud Mental, CIBERSAM (Biomedical Network Research Center of Mental Health), Institute of Health Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1lvaro G.","family":"Bris","sequence":"additional","affiliation":[{"name":"Departamento de Farmacolog\u00eda y Toxicolog\u00eda, Facultad de Medicina, Universidad Complutense de Madrid, Instituto de Investigaci\u00f3n Sanitaria Hospital 12 de Octubre (Imas12), Instituto Universitario de Investigaci\u00f3n en Neuroqu\u00edmica IUIN-UCM, Avda. Complutense s\/n, 28040 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Salud Mental, CIBERSAM (Biomedical Network Research Center of Mental Health), Institute of Health Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8622-749X","authenticated-orcid":false,"given":"Javier R.","family":"Caso","sequence":"additional","affiliation":[{"name":"Departamento de Farmacolog\u00eda y Toxicolog\u00eda, Facultad de Medicina, Universidad Complutense de Madrid, Instituto de Investigaci\u00f3n Sanitaria Hospital 12 de Octubre (Imas12), Instituto Universitario de Investigaci\u00f3n en Neuroqu\u00edmica IUIN-UCM, Avda. Complutense s\/n, 28040 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Salud Mental, CIBERSAM (Biomedical Network Research Center of Mental Health), Institute of Health Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1005-1739","authenticated-orcid":false,"given":"Judit","family":"Vill\u00e9n","sequence":"additional","affiliation":[{"name":"Department of Genome Sciences, School of Medicine, University of Washington, 3720 15th Ave NE, Seattle, WA 98195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4577-2106","authenticated-orcid":false,"given":"Bel\u00e9n","family":"Ramos","sequence":"additional","affiliation":[{"name":"Psiquiatria Molecular, Institut de Recerca Sant Joan de D\u00e9u, Santa Rosa 39\u201357, 08950 Esplugues de Llobregat, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Salud Mental, CIBERSAM (Biomedical Network Research Center of Mental Health), Institute of Health Carlos III, 28029 Madrid, Spain"},{"name":"Parc Sanitari Sant Joan de D\u00e9u, Doctor Antoni Pujadas 42, 08830 Sant Boi de Llobregat, Spain"},{"name":"Faculty of Medicine, University of Vic\u2014Central University of Catalonia, 08500 Vic, Spain"},{"name":"Departamento de Bioqu\u00edmica i Biolog\u00eda Molecular, Facultat de Medicina, Universitat Aut\u00f2noma de Barcelona, 08193 Bellaterra, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1038\/s41380-019-0436-y","article-title":"Combined cellomics and proteomics analysis reveals shared neuronal morphology and molecular pathway phenotypes for multiple schizophrenia risk genes","volume":"26","author":"Rosato","year":"2021","journal-title":"Mol. 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