| First Author | Kanemoto S | Year | 2014 |
| Journal | Neuroscience | Volume | 261 |
| Pages | 52-9 | PubMed ID | 24361736 |
| Mgi Jnum | J:208010 | Mgi Id | MGI:5560424 |
| Doi | 10.1016/j.neuroscience.2013.12.021 | Citation | Kanemoto S, et al. (2014) Proliferation, differentiation and amyloid-beta production in neural progenitor cells isolated from TgCRND8 mice. Neuroscience 261:52-9 |
| abstractText | The amyloid precursor protein (APP) and amyloid-beta (Abeta) peptide play central roles in the pathology and etiology of Alzheimer's 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 Abeta 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 Abeta production as well as amyloid deposition in 5-week-old TgCRND8 mice, which are well-established Alzheimer's 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 8weeks. 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/S100beta 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 Abeta peptides. This suggests that the proliferation of neural progenitors in vivo may be modulated by high levels of APP expression and the resulting Abeta generated directly by the progenitor cells. These findings indicate that cell proliferation is increased prior to Abeta deposition and that cell viability is decreased in TgCRND8 mice over time. |
