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

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 chrom...

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Autores: Vera Montecinos, América, Rodríguez Mias, Ricard, Mac-Dowell Mata, Karina Soledad, García Bueno, Borja, González Bris, Álvaro, Caso Fernández, Javier Rubén, Villén, Judit, Ramos, Belén
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/4839
Acceso en línea:https://hdl.handle.net/20.500.14352/4839
Access Level:acceso abierto
Palabra clave:Proteomics
Postmortem brain
Pathways
Networks
Schizophrenia
Fisiología
Neurociencias (Medicina)
Psiquiatría
2411 Fisiología Humana
2490 Neurociencias
3211 Psiquiatría
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spelling Analysis of Molecular Networks in the Cerebellum in Chronic Schizophrenia: Modulation by Early Postnatal Life Stressors in Murine ModelsVera Montecinos, AméricaRodríguez Mias, RicardMac-Dowell Mata, Karina SoledadGarcía Bueno, BorjaGonzález Bris, ÁlvaroCaso Fernández, Javier RubénVillén, JuditRamos, BelénProteomicsPostmortem brainPathwaysNetworksSchizophreniaFisiologíaNeurociencias (Medicina)Psiquiatría2411 Fisiología Humana2490 Neurociencias3211 PsiquiatríaDespite 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.MPDIUniversidad Complutense de Madrid20212021-09-1720212021-09-17journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.14352/4839reponame:Docta Complutenseinstname:Universidad Complutense de Madrid (UCM)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Atribución 3.0 Españahttps://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:docta.ucm.es:20.500.14352/48392026-06-02T12:44:21Z
dc.title.none.fl_str_mv Analysis of Molecular Networks in the Cerebellum in Chronic Schizophrenia: Modulation by Early Postnatal Life Stressors in Murine Models
title Analysis of Molecular Networks in the Cerebellum in Chronic Schizophrenia: Modulation by Early Postnatal Life Stressors in Murine Models
spellingShingle Analysis of Molecular Networks in the Cerebellum in Chronic Schizophrenia: Modulation by Early Postnatal Life Stressors in Murine Models
Vera Montecinos, América
Proteomics
Postmortem brain
Pathways
Networks
Schizophrenia
Fisiología
Neurociencias (Medicina)
Psiquiatría
2411 Fisiología Humana
2490 Neurociencias
3211 Psiquiatría
title_short Analysis of Molecular Networks in the Cerebellum in Chronic Schizophrenia: Modulation by Early Postnatal Life Stressors in Murine Models
title_full Analysis of Molecular Networks in the Cerebellum in Chronic Schizophrenia: Modulation by Early Postnatal Life Stressors in Murine Models
title_fullStr Analysis of Molecular Networks in the Cerebellum in Chronic Schizophrenia: Modulation by Early Postnatal Life Stressors in Murine Models
title_full_unstemmed Analysis of Molecular Networks in the Cerebellum in Chronic Schizophrenia: Modulation by Early Postnatal Life Stressors in Murine Models
title_sort Analysis of Molecular Networks in the Cerebellum in Chronic Schizophrenia: Modulation by Early Postnatal Life Stressors in Murine Models
dc.creator.none.fl_str_mv Vera Montecinos, América
Rodríguez Mias, Ricard
Mac-Dowell Mata, Karina Soledad
García Bueno, Borja
González Bris, Álvaro
Caso Fernández, Javier Rubén
Villén, Judit
Ramos, Belén
author Vera Montecinos, América
author_facet Vera Montecinos, América
Rodríguez Mias, Ricard
Mac-Dowell Mata, Karina Soledad
García Bueno, Borja
González Bris, Álvaro
Caso Fernández, Javier Rubén
Villén, Judit
Ramos, Belén
author_role author
author2 Rodríguez Mias, Ricard
Mac-Dowell Mata, Karina Soledad
García Bueno, Borja
González Bris, Álvaro
Caso Fernández, Javier Rubén
Villén, Judit
Ramos, Belén
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidad Complutense de Madrid
dc.subject.none.fl_str_mv Proteomics
Postmortem brain
Pathways
Networks
Schizophrenia
Fisiología
Neurociencias (Medicina)
Psiquiatría
2411 Fisiología Humana
2490 Neurociencias
3211 Psiquiatría
topic Proteomics
Postmortem brain
Pathways
Networks
Schizophrenia
Fisiología
Neurociencias (Medicina)
Psiquiatría
2411 Fisiología Humana
2490 Neurociencias
3211 Psiquiatría
description 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.
publishDate 2021
dc.date.none.fl_str_mv 2021
2021-09-17
2021
2021-09-17
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.14352/4839
url https://hdl.handle.net/20.500.14352/4839
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 3.0 España
https://creativecommons.org/licenses/by/3.0/es/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 3.0 España
https://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MPDI
publisher.none.fl_str_mv MPDI
dc.source.none.fl_str_mv reponame:Docta Complutense
instname:Universidad Complutense de Madrid (UCM)
instname_str Universidad Complutense de Madrid (UCM)
reponame_str Docta Complutense
collection Docta Complutense
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300724

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