Chronic mild stress-induced alterations of clock gene expression in rat prefrontal cortex: modulatory effects of prolonged lurasidone treatment.
Pharmacol Res
; 104: 140-50, 2016 Feb.
Article
em En
| MEDLINE
| ID: mdl-26742719
ABSTRACT
Disruptions of biological rhythms are known to be associated with depressive disorders, suggesting that abnormalities in the molecular clock may contribute to the development of these disorders. These mechanisms have been extensively characterized in the suprachiasmatic nucleus, but little is know about the role exerted by individual clock genes in brain structures that are important for depressive disorders. Using the chronic mild stress model we found a significant reduction of BMAL1 and CLOCK protein levels in the nuclear compartment of the prefrontal cortex of CMS rats, which was paralleled by a down-regulation of the expression of several target genes, including Pers and Crys but also Reverbß and Pparα. Interestingly, chronic treatment with the multi receptor modulator lurasidone (3mg/kg for 5 weeks) was able to normalize the molecular changes induced by CMS exposure in prefrontal cortex, but it was also able to regulate some of these genes within the hippocampus. We believe that changes in clock genes expression after CMS exposure may contribute to the disturbances associated with depressive disorders and that the ability of chronic lurasidone to normalize such alterations may be relevant for its therapeutic properties in ameliorating functions that are deteriorated in patients with major depression and other stress-related disorders.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Estresse Psicológico
/
Córtex Pré-Frontal
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Peptídeos e Proteínas de Sinalização do Ritmo Circadiano
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Cloridrato de Lurasidona
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Pharmacol Res
Ano de publicação:
2016
Tipo de documento:
Article