Calcium-binding proteins are altered in the cerebellum in schizophrenia
Vidal-Domènech, Francisco (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Riquelme, Gemma (Institut de Recerca Sant Joan de Déu)
Pinacho, Raquel (Institut de Recerca Sant Joan de Déu)
Rodríguez-Mias, Ricard (University of Washington)
Vera, América (Institut de Recerca Sant Joan de Déu)
Monje, Alfonso (Parc Sanitari Sant Joan de Déu)
Ferrer, Isidro (Institut d'Investigació Biomèdica de Bellvitge)
Callado, Luis F. (Instituto de Investigación Sanitaria Biocruces Bizkaia)
Meana, J. Javier (Instituto de Investigación Sanitaria Biocruces Bizkaia)
Villén, Judit (University of Washington)
Ramos, Belén (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)

Data:	2020
Resum:	Alterations in the cortico-cerebellar-thalamic-cortical circuit might underlie the diversity of symptoms in schizophrenia. However, molecular changes in cerebellar neuronal circuits, part of this network, have not yet been fully determined. Using LC-MS/MS, we screened altered candidates in pooled grey matter of cerebellum from schizophrenia subjects who committed suicide (n = 4) and healthy individuals (n = 4). Further validation by immunoblotting of three selected candidates was performed in two cohorts comprising schizophrenia (n = 20), non-schizophrenia suicide (n = 6) and healthy controls (n = 21). We found 99 significantly altered proteins, 31 of them previously reported in other brain areas by proteomic studies. Transport function was the most enriched category, while cell communication was the most prevalent function. For validation, we selected the vacuolar proton pump subunit 1 (VPP1), from transport, and two EF-hand calcium-binding proteins, calmodulin and parvalbumin, from cell communication. All candidates showed significant changes in schizophrenia (n = 7) compared to controls (n = 7). VPP1 was altered in the non-schizophrenia suicide group and increased levels of parvalbumin were linked to antipsychotics. Further validation in an independent cohort of non-suicidal chronic schizophrenia subjects (n = 13) and non-psychiatric controls (n = 14) showed that parvalbumin was increased, while calmodulin was decreased in schizophrenia. Our findings provide evidence of calcium-binding protein dysregulation in the cerebellum in schizophrenia, suggesting an impact on normal calcium-dependent synaptic functioning of cerebellar circuits. Our study also links VPP1 to suicide behaviours, suggesting a possible impairment in vesicle neurotransmitter refilling and release in these phenotypes.
Ajuts:	Instituto de Salud Carlos III MS16/00153 Agencia Estatal de Investigación SAF2017-88126-R Instituto de Salud Carlos III CP16/00153
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
Publicat a:	PloS one, Vol. 15, Num. 7 (July 2020) , art. e0230400, ISSN 1932-6203

DOI: 10.1371/journal.pone.0230400
PMID: 32639965

22 p, 1.2 MB

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