Smoothened agonist augments proliferation and survival of neural cells.
Neurosci Lett
; 482(2): 81-5, 2010 Sep 27.
Article
em En
| MEDLINE
| ID: mdl-20600593
ABSTRACT
Sonic hedgehog signaling pathway is important in developmental processes like dorsoventral neural tube patterning, neural stem cell proliferation and neuronal and glial cell survival. Shh is also implicated in the regulation of the adult hippocampal neurogenesis. Recently, nonpeptidyl Smoothened activators of the Shh pathway have been identified. The aim of this study was to investigate the effects of chlorobenzothiophene-containing molecule, Smo agonist (SAG), which has been shown to activate Shh signaling pathway, in neurogenesis and neuronal survival in in vitro and in vivo models. Our in vitro experiments showed that SAG induces increased expression of Gli1 mRNA, transcriptional target and mediator of Shh signal. In vitro experiments also demonstrated that SAG in low-nanomolar concentrations induces proliferation of neuronal and glial precursors without affecting the differentiation pattern of newly produced cells. In contrast to Shh, SAG did not induce neurotoxicity in neuronal cultures. The SAG and Shh treatment also promoted the survival of newly generated neural cells in the dentate gyrus after their intracerebroventricular administration to adult rats. We propose that SAG and similar compounds represent attractive molecules to be developed for treatment of disorders where stimulation of the generation and survival of new neural cells would be beneficial.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Tiofenos
/
Cicloexilaminas
/
Receptores Acoplados a Proteínas G
/
Neurônios
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Neurosci Lett
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Estônia