S-Space College of Veterinary Medicine (수의과대학) Dept. of Veterinary Medicine (수의학과) Journal Papers (저널논문_수의학과)
Impaired functions of neural stem cells by abnormal nitric oxide-mediated signaling in an in vitro model of Niemann-Pick type C disease
|dc.contributor.author||Kang, Soo Kyung||-|
|dc.contributor.author||Lee, Yong Soon||-|
|dc.identifier.citation||Cell Res 2008; 18:686-694||en|
|dc.description.abstract||Nitric oxide (NO) has been implicated in the promotion of neurodegeneration. However, little is known about the relationship between NO and the self-renewal or differentiation capacity of neural stem cells (NSCs) in neurodegenerative disease. In this study, we investigated the effect of NO on self-renewal of NSCs in an animal model for Niemann-Pick type C (NPC) disease. We found that NO production was significantly increased in NSCs from NPC1-deficient mice (NPC1- /- ), which showed reduced NSC self-renewal. The number of nestin-positive cells and the size of neurospheres were both significantly decreased. The expression of NO synthase (NOS) was increased in neurospheres derived from the brain of NPC1- /- mice in comparison to wild-type neurospheres. NO-mediated activation of glycogen synthase kinase-3 (GSK3) and caspase-3 was also observed in NSCs from NPC1- /- mice. The self-renewal ability of NSCs from NPC1- /- mice was restored by an NOS inhibitor, L-NAME, which resulted in the inhibition of GSK3 and caspase-3. In addition, the differentiation ability of NSCs was partially restored and the number of Fluoro-Jade C-positive degenerating neurons was reduced. These data suggest that overproduction of NO in NPC disease impaired the self-renewal of NSCs. Control of NO production may be key for the treatment of NPC disease.||en|
|dc.description.sponsorship||This work was supported by a grant from the Korean
Science & Engineering Foundation (R01-2005-000-10190-0)
and the BK21 Program for Veterinary Science.
|dc.publisher||Nature Publishing Group||en|
|dc.subject||neural stem cells||en|
|dc.subject||Niemann-Pick type C1 disease||en|
|dc.title||Impaired functions of neural stem cells by abnormal nitric oxide-mediated signaling in an in vitro model of Niemann-Pick type C disease||en|
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