Hypoxia activates glycogen synthase kinase-3 in mouse brain in vivo: protection by mood stabilizers and imipramine.
Biol Psychiatry
; 57(3): 278-86, 2005 Feb 01.
Article
em En
| MEDLINE
| ID: mdl-15691529
ABSTRACT
BACKGROUND:
Glycogen synthase kinase-3 (GSK3), which is primarily regulated by an inhibitory phosphorylation of an N-terminal serine, has been implicated as contributing to mood disorders by the finding that it is inhibited by the mood stabilizer lithium.METHODS:
This study tested if the antidepressant imipramine or the mood stabilizers lithium and sodium valproate regulated pathophysiological serine-dephosphorylation of GSK3 caused by hypoxia in mouse brain in vivo.RESULTS:
Hypoxia caused rapid serine-dephosphorylation of both isoforms of GSK3, GSK3beta and GSK3alpha, in mouse cerebral cortex, hippocampus, and striatum. Pretreatment of mice with imipramine, sodium valproate, or lithium attenuated hypoxia-induced serine-dephosphorylation of GSK3beta and GSK3alpha in all three brain regions.CONCLUSIONS:
These results demonstrate that imipramine and mood stabilizers are capable of blocking pathophysiologically induced serine-dephosphorylation of GSK3, supporting the hypothesis that stabilization of serine-phosphorylation of GSK3 contributes to their therapeutic effects.
Buscar no Google
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Encéfalo
/
Quinase 3 da Glicogênio Sintase
/
Imipramina
/
Lítio
/
Hipóxia
/
Antidepressivos Tricíclicos
Limite:
Animals
Idioma:
En
Revista:
Biol Psychiatry
Ano de publicação:
2005
Tipo de documento:
Article
País de afiliação:
Estados Unidos