Disrupted-in-schizophrenia 1 functional polymorphisms and D2 /D3 receptor availability: A [11 C]-(+)-PHNO imaging study.
Genes Brain Behav
; 18(8): e12596, 2019 11.
Article
em En
| MEDLINE
| ID: mdl-31264367
ABSTRACT
The disrupted-in-schizophrenia 1 (DISC1) protein has been implicated in a range of biological mechanisms underlying chronic mental disorders such as schizophrenia. Schizophrenia is associated with abnormal striatal dopamine signalling, and all antipsychotic drugs block striatal dopamine 2/3 receptors (D2/3 Rs). Importantly, the DISC1 protein directly interacts and forms a protein complex with the dopamine D2 receptor (D2 R) that inhibits agonist-induced D2 R internalisation. Moreover, animal studies have found large striatal increases in the proportion of D2 R receptors in a high affinity state (D2high R) in DISC1 rodent models. Here, we investigated the relationship between the three most common polymorphisms altering the amino-acid sequence of the DISC1 protein (Ser704Cys (rs821616), Leu607Phe (rs6675281) and Arg264Gln (rs3738401)) and striatal D2/3 R availability in 41 healthy human volunteers, using [11 C]-(+)-PHNO positron emission tomography. We found no association between DISC1 polymorphisms and D2/3 R availability in the striatum and D2 R availability in the caudate and putamen. Therefore, despite a direct interaction between DISC1 and the D2 R, none of its main functional polymorphisms impact striatal D2/3 R binding potential, suggesting DISC1 variants act through other mechanisms.
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Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Receptores Dopaminérgicos
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Corpo Estriado
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Polimorfismo de Nucleotídeo Único
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Proteínas do Tecido Nervoso
Limite:
Adult
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Female
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Humans
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Male
Idioma:
En
Revista:
Genes Brain Behav
Assunto da revista:
CIENCIAS DO COMPORTAMENTO
/
GENETICA
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Reino Unido