Calcium-binding proteins are altered in the cerebellum in schizophrenia.
Adult
Calcium-Binding Proteins
/ metabolism
Calmodulin
/ metabolism
Case-Control Studies
Cerebellum
/ metabolism
Chromatography, High Pressure Liquid
Down-Regulation
Female
Humans
Male
Middle Aged
Parvalbumins
/ metabolism
Proteome
/ analysis
Schizophrenia
/ metabolism
Suicide, Attempted
Tandem Mass Spectrometry
Up-Regulation
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2020
2020
Historique:
received:
24
02
2020
accepted:
17
06
2020
entrez:
9
7
2020
pubmed:
9
7
2020
medline:
8
9
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32639965
doi: 10.1371/journal.pone.0230400
pii: PONE-D-20-05318
pmc: PMC7343173
doi:
Substances chimiques
Calcium-Binding Proteins
0
Calmodulin
0
Parvalbumins
0
Proteome
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0230400Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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