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Analysis of Molecular Networks in the Cerebellum in Chronic Schizophrenia: Modulation by Early Postnatal Life Stressors in Murine Models

dc.contributor.authorVera Montecinos, América
dc.contributor.authorRodríguez Mias, Ricard
dc.contributor.authorMac-Dowell Mata, Karina Soledad
dc.contributor.authorGarcía Bueno, Borja
dc.contributor.authorGonzález Bris, Álvaro
dc.contributor.authorCaso Fernández, Javier Rubén
dc.contributor.authorVillén, Judit
dc.contributor.authorRamos, Belén
dc.date.accessioned2023-06-16T14:22:05Z
dc.date.available2023-06-16T14:22:05Z
dc.date.issued2021-09-17
dc.description.abstractDespite 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.en
dc.description.departmentDepto. de Farmacología y Toxicología
dc.description.departmentDepto. de Medicina
dc.description.facultyFac. de Medicina
dc.description.refereedTRUE
dc.description.sponsorshipMinisterio de Economía, Comercio y Empresa (España)
dc.description.sponsorshipInstituto de Salud Carlos III
dc.description.sponsorshipInstituto de Salud Carlos III/Fondo Europeo de Desarrollo Regional
dc.description.sponsorshipComisión Nacional de Investigación Científica y Tecnológica (Chile)
dc.description.sponsorshipNational Institutes of Health
dc.description.statuspub
dc.eprint.idhttps://eprints.ucm.es/id/eprint/71677
dc.identifier.citationVera Montecinos, A., Rodríguez Mias, R., MacDowell, K. S. et al. «Analysis of Molecular Networks in the Cerebellum in Chronic Schizophrenia: Modulation by Early Postnatal Life Stressors in Murine Models». International Journal of Molecular Sciences, vol. 22, n.o 18, septiembre de 2021, p. 10076. DOI.org (Crossref), https://doi.org/10.3390/ijms221810076.
dc.identifier.doi10.3390/ijms221810076
dc.identifier.issn1422-0067
dc.identifier.officialurlhttps://doi.org/10.3390/ijms221810076
dc.identifier.relatedurlhttps://www.mdpi.com/1422-0067/22/18/10076/htm
dc.identifier.urihttps://hdl.handle.net/20.500.14352/4839
dc.issue.number18
dc.journal.titleInternational Journal of Molecular Sciences
dc.language.isoeng
dc.page.initial10076
dc.publisherMPDI
dc.relation.projectIDSAF2016-75500R
dc.relation.projectIDMiguel Servet grant (MS16/00153-CP16/00153 to BR)
dc.relation.projectID(PI18/00213)
dc.relation.projectID(72160426)
dc.relation.projectID(R35GM119536 and R01NS098329)
dc.rightsAtribución 3.0 España
dc.rights.accessRightsopen access
dc.rights.urihttps://creativecommons.org/licenses/by/3.0/es/
dc.subject.keywordProteomics
dc.subject.keywordPostmortem brain
dc.subject.keywordPathways
dc.subject.keywordNetworks
dc.subject.keywordSchizophrenia
dc.subject.ucmFisiología
dc.subject.ucmNeurociencias (Medicina)
dc.subject.ucmPsiquiatría
dc.subject.unesco2411 Fisiología Humana
dc.subject.unesco2490 Neurociencias
dc.subject.unesco3211 Psiquiatría
dc.titleAnalysis of Molecular Networks in the Cerebellum in Chronic Schizophrenia: Modulation by Early Postnatal Life Stressors in Murine Modelsen
dc.typejournal article
dc.volume.number22
dspace.entity.typePublication
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relation.isAuthorOfPublication.latestForDiscovery0c44d00b-2f15-4375-9aba-bbd0b931fcf4

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