Selective vulnerability of different types of commissural neurons for amyloid β-protein-induced neurodegeneration in APP23 mice correlates with dendritic tree morphology
Selective vulnerability of different types of commissural neurons for amyloid β-protein-induced neurodegeneration in APP23 mice correlates with dendritic tree morphology
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DOI：
10.1093/brain/awl176
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发表时间：
2006-11-01
期刊：
影响因子：
14.5
通讯作者：
Thal, Dietmar Rudolf
中科院分区：
文献类型：
--
作者：
Capetillo-Zarate, Estibaliz;Staufenbiel, Matthias;Thal, Dietmar Rudolf
淀粉样蛋白（A β）是阿尔茨海默病相关老年斑的主要成分。尽管A - β与阿尔茨海默病的发展有关，但尚未显示出哪种形式的A - β在体内诱导神经变性，以及哪种类型的神经元易受伤害。为了解决这些问题，我们将DiI晶体植入过表达突变人类淀粉样前体蛋白基因（APP）的APP23转基因小鼠和同窝对照小鼠的左额中央皮层。对3、5、11、15月龄小鼠右侧额中央皮层第3层追踪的联合神经元进行定量分析。三种不同类型的联合神经元被追踪。在3月龄时，与野生型小鼠相比，APP23小鼠标记的联合神经元数量没有差异。与野生型动物相比，在5、11和15月龄时，APP23小鼠的重度分支型神经元选择性减少，从5月龄时前额中央皮层出现第一次A - β沉积开始。另外两种类型的联合神经元在5个月和11个月时没有表现出变化。在15个月时，与野生型小鼠相比，APP23小鼠追踪到的稀疏分支锥体神经元的数量除了严重分支神经元的数量外，还减少了。此时，在新皮层和异位皮层以及基底神经节和丘脑中可以看到A - β沉积。总之，我们的结果表明，A β诱导不同类型的联合神经元进行性变性。最脆弱的神经元的退化与新皮层中第一个纤维状A - β沉积的发生同时开始，即与聚集的A - β的检测同时开始。额外的神经元亚群的参与与A - β沉积扩展到更远的大脑区域有关。因此，不同类型的神经元对A β的脆弱性可能与它们树突形态的复杂性有关。
The amyloid beta-protein (A beta) is the main component of Alzheimer's disease-related senile plaques. Although A beta is associated with the development of Alzheimer's disease, it has not been shown which forms of A beta induce neurodegeneration in vivo and which types of neurons are vulnerable. To address these questions, we implanted DiI crystals into the left frontocentral cortex of APP23 transgenic mice overexpressing mutant human APP (amyloid precursor protein gene) and of littermate controls. Traced commissural neurons in layer III of the right frontocentral cortex were quantified in 3-, 5-, 11- and 15-month-old mice. Three different types of commissural neurons were traced. At 3 months of age no differences in the number of labelled commissural neurons were seen in APP23 mice compared with wild-type mice. A selective reduction of the heavily ramified type of neurons was observed in APP23 mice compared with wild-type animals at 5, 11 and 15 months of age, starting when the first A beta-deposits occurred in the frontocentral cortex at 5 months. The other two types of commissural neurons did not show alterations at 5 and 11 months. At 15 months, the number of traced sparsely ramified pyramidal neurons was reduced in addition to that of the heavily ramified neurons in APP23 mice compared with wild-type mice. At this time A beta-deposits were seen in the neo- and allocortex as well as in the basal ganglia and the thalamus. In summary, our results show that A beta induces progressive degeneration of distinct types of commissural neurons. Degeneration of the most vulnerable neurons starts in parallel with the occurrence of the first fibrillar A beta-deposits in the neocortex, that is, with the detection of aggregated A beta. The involvement of additional neuronal subpopulations is associated with the expansion of A beta-deposition into further brain regions. The vulnerability of different types of neurons to A beta, thereby, is presumably related to the complexity of their dendritic morphology.