期刊
INTERNATIONAL JOURNAL OF NEUROSCIENCE
卷 126, 期 3, 页码 257-268出版社
TAYLOR & FRANCIS LTD
DOI: 10.3109/00207454.2015.1008696
关键词
alzheimer's disease; nicotine; neural stem cell; (alpha 7)-nAChR; beta-catenin
资金
- National Natural Science Foundation of China [30471928, 30973162]
- Natural Science Foundation of Guangdong Province [04020430]
Recent studies have demonstrated that the molecules secreted from microglias play important roles in the cell fate determination of neural stem cells (NSCs), and nicotinic acetylcholine receptor agonist treatment could reduce neuroinflammation in some neurodegenerative disease models, such as Alzheimer's disease (AD). However, it is not clear how nicotine plays a neuroprotective role in inflammation-mediated central nervous diseases, and its possible mechanisms in the process remain largely elusive. The aim of this study is to improve the survival microenvironment of NSCs co-cultured with microglias in vitro by weakening inflammation that mediated by accumulation of -amyloid peptide (A). The viability, proliferation, differentiation, apoptosis of NSCs and underlying mechanisms associated with Wnt signaling pathway were investigated. The results showed that A could directly damage NSCs. Furthermore, concomitant to elevated levels of TNF-, IL-1 derived from microglias, the NSCs had been damaged more severely with the upregulation of Axin 2, p--catenin and the downregulation of -catenin, p-GSK-3, microtubule-associated protein-2, choline acetyltransferase. However, addition of 10mol/L nicotine before microglias treated with A was beneficial to protect the NSCs against neurotoxicity of microglial-derived factors induced by A, which partially rescued proliferation, differentiation and inhibited apoptosis of NSCs via activation of Wnt/-catenin pathway. Taken together, these data imply that low concentration nicotine attenuates NSCs injury induced by microglial-derived factors via Wnt signaling pathway. Thus, treatment with nicotinic acetylcholine receptor agonist provides a promising research field for neural stem cell fate and therapeutic intervention in neuroinflammation diseases.
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