We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
IKK?/NF-?B disrupts adult hypothalamic neural stem cells to mediate a neurodegenerative mechanism of dietary obesity and pre-diabetes.
- Authors
Li, Juxue; Tang, Yizhe; Cai, Dongsheng
- Abstract
Adult neural stem cells (NSCs) are known to exist in a few regions of the brain; however, the entity and physiological/disease relevance of adult hypothalamic NSCs (htNSCs) remain unclear. This work shows that adult htNSCs are multipotent and predominantly present in the mediobasal hypothalamus of adult mice. Chronic high-fat-diet feeding led to not only depletion but also neurogenic impairment of htNSCs associated with IKK?/NF-?B activation. In vitro htNSC models demonstrated that their survival and neurogenesis markedly decreased on IKK?/NF-?B activation but increased on IKK?/NF-?B inhibition, mechanistically mediated by IKK?/NF-?B-controlled apoptosis and Notch signalling. Mouse studies revealed that htNSC-specific IKK?/NF-?B activation led to depletion and impaired neuronal differentiation of htNSCs, and ultimately the development of obesity and pre-diabetes. In conclusion, adult htNSCs are important for the central regulation of metabolic physiology, and IKK?/NF-?B-mediated impairment of adult htNSCs is a critical neurodegenerative mechanism for obesity and related diabetes.
- Subjects
NEURAL stem cells; NEURODEGENERATION; HYPOTHALAMUS; OBESITY; DIABETES; APOPTOSIS; LABORATORY mice
- Publication
Nature Cell Biology, 2012, Vol 14, Issue 10, p999
- ISSN
1465-7392
- Publication type
Article
- DOI
10.1038/ncb2562