Proliferation, differentiation and amyloid-β production in neural progenitor cells isolated from TgCRND8 mice.
Proliferation, differentiation and amyloid-β production in neural progenitor cells isolated from TgCRND8 mice.
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DOI：
10.1016/j.neuroscience.2013.12.021
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发表时间：
2014-03-07
期刊：
影响因子：
3.3
通讯作者：
Fraser, P. E.
中科院分区：
文献类型：
--
作者：
Kanemoto, S.;Griffin, J.;Markham-Coultes, K.;Aubert, I.;Tandon, A.;George-Hyslop, P. S.;Fraser, P. E.
在年轻TgCRND8小鼠中，与非tg对照小鼠相比，齿状回新生细胞的增殖增加。相反，TgCRND8海马新生细胞向神经祖细胞的分化受到损害。从TgCRND8小鼠海马中分离的神经球培养物的活力低于非tg对照组。TgCRND8小鼠的神经球培养物分泌高水平的Aβ肽。淀粉样蛋白前体蛋白（APP）和淀粉样蛋白β (Aβ)肽在阿尔茨海默病的病理和病因学中起核心作用。淀粉样蛋白诱导的神经发生损伤已经在几种转基因小鼠模型中进行了研究，但其作用机制仍有待最终证实。本研究探讨了Aβ水平升高和斑块形成的转变过程中神经发生的变化。我们发现，与非转基因（非tg）小鼠相比，5周大的TgCRND8小鼠（已建立的阿尔茨海默病模型）齿状回中新生细胞的增殖在可溶性Aβ生成和淀粉样蛋白沉积升高之前增强。在8周的时间里，TgCRND8小鼠的brdu阳性细胞数量仍然高于非tg小鼠。与非tg小鼠相比，TgCRND8中BrdU/ neun阳性细胞的数量无显著差异。在6周龄时，Tg组与非Tg组相比，BrdU/GFAP显著降低，但BrdU/S100β未显著降低。此外，使用TgCRND8小鼠分离的神经祖细胞进行了独特的观察，发现其在培养中存活率较低，并产生大量分泌的a β肽。这表明，体内神经祖细胞的增殖可能受高水平的APP表达和由此产生的由祖细胞直接产生的Aβ的调节。这些发现表明，随着时间的推移，TgCRND8小鼠的细胞增殖在Aβ沉积之前增加，细胞活力下降。
In young TgCRND8 mice, proliferation of newborn cells in dentate gyrus is increased, compared with Non-Tg control mice. On the contrary, differentiation to neural progenitor cells of newborn cells in the TgCRND8 hippocampus is impaired. Neurosphere cultures isolated from hippocampi of TgCRND8 mice show low viability than those from Non-Tg control. Neurosphere cultures from TgCRND8 mice secrete high levels of Aβ peptide. The amyloid precursor protein (APP) and amyloid-β (Aβ) 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 Aβ 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 Aβ 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 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/S100β 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 Aβ peptides. This suggests that the proliferation of neural progenitors in vivo may be modulated by high levels of APP expression and the resulting Aβ generated directly by the progenitor cells. These findings indicate that cell proliferation is increased prior to Aβ deposition and that cell viability is decreased in TgCRND8 mice over time.
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影响因子：
16.6
作者：
Niibori, Yosuke;Yu, Tzong-Shiue;Frankland, Paul W.
通讯作者：
Frankland, Paul W.
影响因子：
5.3
作者：
Rochefort, C;Gheusi, G;Lledo, PM
通讯作者：
Lledo, PM
影响因子：
4.8
作者：
Beher, D;Wrigley, JDJ;Shearman, MS
通讯作者：
Shearman, MS
DOI：
10.1523/jneurosci.2775-12.2012
发表时间：
2012-11-14
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Lauritzen I;Pardossi-Piquard R;Bauer C;Brigham E;Abraham JD;Ranaldi S;Fraser P;St-George-Hyslop P;Le Thuc O;Espin V;Chami L;Dunys J;Checler F
通讯作者：
Checler F
影响因子：
14.8
作者：
Kee, Nohjin;Teixeira, Catia M.;Frankland, Paul W.
通讯作者：
Frankland, Paul W.