Analysis of molecular networks in the cerebellum in chronic schizophrenia : modulation by early postnatal life stressors in murine models
Vera-Montecinos, América (Institut de Recerca Sant Joan de Déu)
Rodríguez-Mias, Ricard (University of Washington. Department of Genome Sciences)
Macdowell, Karina S. (Centro de Investigación Biomédica en Red de Salud Mental)
García-Bueno, Borja (Centro de Investigación Biomédica en Red de Salud Mental)
Bris, Álvaro (Centro de Investigación Biomédica en Red de Salud Mental)
Caso, Javier R. (Centro de Investigación Biomédica en Red de Salud Mental)
Villén, Judit (University of Washington. Department of Genome Sciences)
Ramos, Belén (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)

Data:	2021
Resum:	Despite the growing importance of the cerebellum as a region highly vulnerable to accumu-lating 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 ProteomeX-change 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.
Ajuts:	Instituto de Salud Carlos III MS16/00153 Ministerio de Economía y Competitividad CP16/00153 Instituto de Salud Carlos III PI18/00213 Ministerio de Economía y Competitividad SAF2016-75500R
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Proteomics ; Postmortem brain ; Pathways ; Networks ; Schizophrenia
Publicat a:	International journal of molecular sciences, Vol. 22, Issue 18 (September 2021) , art. 10076, ISSN 1422-0067

DOI: 10.3390/ijms221810076
DOI: 10.1101/2021.02.21.432145
PMID: 34576238

22 p, 13.8 MB

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