Differential cell proliferation in the cortex of the appsweps1de9 alzheimer's disease mouse model
Differential cell proliferation in the cortex of the appsweps1de9 alzheimer's disease mouse model
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DOI：
10.1002/glia.22295
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发表时间：
2012-04-01
期刊：
影响因子：
6.2
通讯作者：
Hol, Elly M.
中科院分区：
文献类型：
--
作者：
Kamphuis, Willem;Orre, Marie;Hol, Elly M.
已知阿尔茨海默病（AD）中的斑块沉积会降低AD小鼠模型中神经原性小生境的增殖，但尚未详细研究对其他脑区细胞增殖和分化的影响。我们分析了不同年龄的野生型（WT）和APPswePS 1dE 9转基因（AD）小鼠皮质中的细胞增殖。在最后一次BrdU注射（BrdU[ST]）后不久对小鼠进行研究。在AD小鼠中，增殖细胞的数量增加了四倍，与斑块的出现及其相关的反应性胶质增生和小胶质细胞的激活相一致。表达活化小胶质细胞标记物的BrdU[ST]-细胞数量的增加是增殖增强的基础。皮质反应性星形胶质细胞没有增殖，因为BrdU[ST]-细胞对不同的星形胶质细胞特异性标志物呈阴性。Olig 2阳性少突胶质前体细胞的数量不变。在最后一次BrdU应用后四周，AD小鼠中具有活化小胶质细胞特征的BrdU[LT]-细胞的数量仍然增加。新生细胞均未分化为少突胶质细胞、星形胶质细胞或神经元。根据这些观察，我们得出结论，淀粉样斑块沉积增加斑块周围的小胶质细胞的增殖，但不影响皮质少突胶质细胞前体细胞的增殖。没有证据表明损伤诱导的反应性星形胶质细胞增殖或室管膜下区的重定向神经发生。小胶质细胞的增殖有助于斑块周围小胶质细胞的快速积聚，并可能在限制斑块扩张中发挥作用。(c)2012 Wiley Periodicals，Inc.
Plaque deposition in Alzheimer's disease (AD) is known to decrease proliferation in neurogenic niches in AD mouse models, but the effects on cell proliferation and differentiation in other brain areas have not been studied in detail. We analyzed cell proliferation in the cortex of wild type (WT) and APPswePS1dE9 transgenic (AD) mice at different ages. Mice were studied shortly after the last BrdU injection (BrdU[ST]). In AD mice, the number of proliferating cells increased fourfold, coinciding with plaque appearance and its associated reactive gliosis and activation of microglia. An increase in the number of BrdU[ST]-cells expressing markers for activated microglia is underlying the enhanced proliferation. Cortical reactive astrocytes did not become proliferative since BrdU[ST]-cells were negative for different astrocyte-specific markers. The number of Olig2-positive oligodendrocyte precursor cells was unchanged. Four weeks after the last BrdU application, the number of BrdU[LT]-cells with an activated microglia signature was still enhanced in AD mice. None of the newborn cells had differentiated into oligodendrocytes, astrocytes, or neurons. On the basis of these observations, we conclude that amyloid plaque deposition increases proliferation of microglia around plaques but does not affect the proliferation of cortical oligodendrocyte precursor cells. No evidence was found for damage-induced proliferation of reactive astrocytes or for a redirected neurogenesis from the subventricular zone. The proliferation of microglia contributes to the rapid accumulation of microglia around plaques and may play a role in limitating plaque expansion. (c) 2012 Wiley Periodicals, Inc.