Cortical copper transporter expression in schizophrenia: interactions of risk gene dysbindin-1.
ATP7A
Alcohol
CTR1
Cognition
Copper
Postmortem
Journal
Journal of neural transmission (Vienna, Austria : 1996)
ISSN: 1435-1463
Titre abrégé: J Neural Transm (Vienna)
Pays: Austria
ID NLM: 9702341
Informations de publication
Date de publication:
05 2021
05 2021
Historique:
received:
16
11
2020
accepted:
28
03
2021
pubmed:
24
4
2021
medline:
12
10
2021
entrez:
23
4
2021
Statut:
ppublish
Résumé
Schizophrenia susceptibility factor dysbindin-1 is associated with cognitive processes. Downregulated dysbindin-1 expression is associated with lower expression of copper transporters ATP7A and CTR1, required for copper transport to the central nervous system. We measured dysbindin-1 isoforms-1A and -1BC, CTR1, and ATP7A via Western blots of the postmortem dorsolateral prefrontal cortex (DLPFC) of schizophrenia subjects (n = 28) and matched controls (n = 14). In addition, we subdivided the schizophrenia group by treatment status and comorbidity of alcohol use disorder (AUD) and assessed the relationships between proteins. Schizophrenia subjects exhibited similar protein levels to that of controls, with no effect of antipsychotic treatment. We observed a shift towards more dysbindin-1A expression in schizophrenia, as revealed by the ratio of dysbindin-1 isoforms. Dysbindin-1A expression was negatively correlated with ATP7A in schizophrenia, with no correlation present in controls. AUD subjects exhibited less dysbindin-1BC and CTR1 than those without AUD. Our results, taken together with previous data, suggest that alterations in dysbindin-1 and copper transporters are brain-region specific. For example, protein levels of ATP7A, dysbindin 1BC, and CTR1 are lower in the substantia nigra in schizophrenia subjects. AUD in the DLPFC was associated with lower protein levels of dysbindin-1 and CTR1. Changes in dysbindin-1 isoform ratio and relationships appear to be prevalent in the disease, potentially impacting symptomology.
Identifiants
pubmed: 33890175
doi: 10.1007/s00702-021-02333-z
pii: 10.1007/s00702-021-02333-z
doi:
Substances chimiques
Antipsychotic Agents
0
Copper Transport Proteins
0
DTNBP1 protein, human
0
Dysbindin
0
Copper
789U1901C5
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
701-709Subventions
Organisme : NINDS NIH HHS
ID : F99NS105208
Pays : United States
Organisme : NIMHD NIH HHS
ID : R21117434
Pays : United States
Organisme : NINDS NIH HHS
ID : F99NS105208
Pays : United States
Organisme : NIMHD NIH HHS
ID : R21117434
Pays : United States
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