Document Detail


Smoothened agonist augments proliferation and survival of neural cells.
MedLine Citation:
PMID:  20600593     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Olga Bragina; Svetlana Sergejeva; Martin Serg; Tamara Zarkovsky; Alla Maloverjan; Priit Kogerman; Aleksandr Zarkovsky
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-07-01
Journal Detail:
Title:  Neuroscience letters     Volume:  482     ISSN:  1872-7972     ISO Abbreviation:  Neurosci. Lett.     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-08-20     Completed Date:  2010-12-06     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7600130     Medline TA:  Neurosci Lett     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  81-5     Citation Subset:  IM    
Copyright Information:
(c) 2010 Elsevier Ireland Ltd. All rights reserved.
Affiliation:
Institute of Clinical Medicine, Tallinn University of Technology, Estonia.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Proliferation
Cell Survival
Cells, Cultured
Cyclohexylamines / pharmacology*
Kruppel-Like Transcription Factors / genetics,  metabolism
Mice
Neurogenesis
Neurons / cytology,  drug effects*
RNA, Messenger / metabolism
Rats
Receptors, G-Protein-Coupled / agonists*
Thiophenes / pharmacology*
Chemical
Reg. No./Substance:
0/Cyclohexylamines; 0/Gli protein, rat; 0/Kruppel-Like Transcription Factors; 0/RNA, Messenger; 0/Receptors, G-Protein-Coupled; 0/SAG compound; 0/Smo protein, mouse; 0/Smo protein, rat; 0/Thiophenes

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