Proliferation, differentiation and amyloid-尾 production in neural progenitor cells isolated from TgCRND8 mice

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• 作者：S. Kanemoto ; J. Griffin ; K. Markham-Coultes ; I. Aubert ; A. T ; on ; P.S. George-Hyslop ; P.E. Fraser
• 关键词：AD ; Alzheimer&rsquo ; s disease ; AICD ; amyloid precursor protein intracellular domain ; ANOVA ; analysis of variance ; APP ; amyloid precursor protein ; A尾 ; amyloid-尾 ; 尾FGF ; fibroblast growth factor ; BrdU ; 5-bromo-2-deoxyuridine ; DMEM ; Dulbecco's modified Eagle medium ; DMSO ; dimethyl sulfoxide ; EGF ; epidermal growth factor ; ELISA ; enzyme-linked immunoabsorbent assay ; FBS ; fetal bovine serum ; GFAP ; glial fibrillary acidic protein ; HRP ; horse radish peroxidase ; NeuN ; neuronal nuclear antigen ; Non-Tg
• 刊名：Neuroscience
• 出版年：7 March, 2014
• 年：2014
• 卷：261
• 期：Complete
• 页码：52-59
• 全文大小：768 K

文摘

The amyloid precursor protein (APP) and amyloid-尾 (A尾) peptide play central roles in the pathology and etiology of Alzheimer鈥檚 disease. Amyloid-induced impairments in neurogenesis have been investigated in several transgenic mouse models but the mechanism of action remains to be conclusively demonstrated. The changes in neurogenesis during this transition of increasing A尾 levels and plaque formation were investigated in the present study. We found that the proliferation of newborn cell in the dentate gyrus was enhanced prior to elevations in soluble A尾 production as well as amyloid deposition in 5-week-old TgCRND8 mice, which are well-established Alzheimer鈥檚 disease models, compared to non-transgenic (Non-Tg) mice. The number of BrdU-positive cells remained higher in TgCRND8 vs Non-Tg mice for a period of 8 weeks. The numbers of BrdU/NeuN-positive cells were not significantly different in TgCRND8 compared to Non-Tg mice. A significant decrease in BrdU/GFAP but not in BrdU/S100尾 was found in Tg vs Non-Tg at 6-weeks of age. In addition, a unique observation was made using isolated neuroprogenitor cells from TgCRND8 mice which were found to be less viable in culture and produced substantial amounts of secreted A尾 peptides. This suggests that the proliferation of neural progenitors in vivo may be modulated by high levels of APP expression and the resulting A尾 generated directly by the progenitor cells. These findings indicate that cell proliferation is increased prior to A尾 deposition and that cell viability is decreased in TgCRND8 mice over time.