Markers of copper transport in the cingulum bundle in schizophrenia.
Copper
DNTBP1
Dysbindin
Myelin
Neurofilament heavy
White matter
α-Tubulin
Journal
Schizophrenia research
ISSN: 1573-2509
Titre abrégé: Schizophr Res
Pays: Netherlands
ID NLM: 8804207
Informations de publication
Date de publication:
02 2021
02 2021
Historique:
received:
26
05
2020
revised:
16
11
2020
accepted:
30
11
2020
pubmed:
13
1
2021
medline:
17
6
2021
entrez:
12
1
2021
Statut:
ppublish
Résumé
Imaging and postmortem studies indicate that schizophrenia subjects exhibit abnormal connectivity in several white matter tracts, including the cingulum bundle. Copper chelators given to experimental animals damage myelin and myelin-producing oligodendrocytes, and the substantia nigra of schizophrenia subjects shows lower levels of copper, copper transporters, and copper-utilizing enzymes. This study aimed to elucidate the potential role of copper homeostasis in white matter pathology in schizophrenia. Protein levels of the copper transporters ATP7A and CTR1, and dysbindin-1, an upstream modulator of copper metabolism and schizophrenia susceptibility factor, were measured using Western blot analyses of the postmortem cingulum bundle of schizophrenia subjects (n=16) and matched controls (n=13). Additionally, the patient group was subdivided by treatment status: off- (n=8) or on-medication (n=8). Relationships between proteins from the current study were correlated among themselves and markers of axonal integrity previously measured in the same cohort. Schizophrenia subjects exhibited similar protein levels to controls, with no effect of antipsychotic treatment. The dysbindin-1A/1BC relationship was positive in controls and schizophrenia subjects; however, antipsychotic treatment appeared to reverse this relationship in a statistically different manner from that of controls and unmedicated subjects. The relationships between dysbindin-1A/neurofilament heavy and ATP7A/α-tubulin were positively correlated in the schizophrenia group that was significantly different from the lack of correlation in controls. Copper transporters and dysbindin-1 appear to be more significantly affected in the grey matter of schizophrenia subjects. However, the relationships among proteins in white matter may be more substantial and dependent on treatment status.
Identifiants
pubmed: 33434726
pii: S0920-9964(20)30636-8
doi: 10.1016/j.schres.2020.11.053
pmc: PMC7988290
mid: NIHMS1661897
pii:
doi:
Substances chimiques
Antipsychotic Agents
0
Copper Transporter 1
0
DTNBP1 protein, human
0
Dysbindin
0
SLC31A1 protein, human
0
Copper
789U1901C5
ATP7A protein, human
EC 7.2.2.8
Copper-Transporting ATPases
EC 7.2.2.8
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
124-133Subventions
Organisme : NINDS NIH HHS
ID : F99 NS105208
Pays : United States
Organisme : NIMH NIH HHS
ID : K00 MH122943
Pays : United States
Organisme : NIMH NIH HHS
ID : R21 MH108867
Pays : United States
Organisme : NIMH NIH HHS
ID : R21 MH117434
Pays : United States
Informations de copyright
Copyright © 2020 Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors have no conflicts of interest to declare.
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