D1 dopamine receptor activation of NFAT-mediated striatal gene expression.
Eur J Neurosci
; 27(1): 31-42, 2008 Jan.
Article
em En
| MEDLINE
| ID: mdl-18184313
ABSTRACT
Exposure to drugs of abuse activates gene expression and protein synthesis that result in long-lasting adaptations in striatal signaling. Therefore, identification of the transcription factors that couple drug exposure to gene expression is of particular importance. Members of the nuclear factor of activated T-cells (NFATc) family of transcription factors have recently been implicated in shaping neuronal function throughout the rodent nervous system. Here we demonstrate that regulation of NFAT-mediated gene expression may also be a factor in drug-induced changes to striatal functioning. In cultured rat striatal neurons, stimulation of D1 dopamine receptors induces NFAT-dependent transcription through activation of L-type calcium channels. Additionally, the genes encoding inositol-1,4,5-trisphosphate receptor type 1 and glutamate receptor subunit 2 are regulated by striatal NFATc4 activity. Consistent with these in-vitro data, repeated exposure to cocaine triggers striatal NFATc4 nuclear translocation and the up-regulation of inositol-1,4,5-trisphosphate receptor type 1 and glutamate receptor subunit 2 gene expression in vivo, suggesting that cocaine-induced increases in gene expression may be partially mediated through activation of NFAT-dependent transcription. Collectively, these findings reveal a novel molecular pathway that may contribute to the enduring modifications in striatal functioning that occur following the administration of drugs of abuse.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Expressão Gênica
/
Receptores de Dopamina D1
/
Corpo Estriado
/
Fatores de Transcrição NFATC
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article