Spatial relationship between synapse loss and β-amyloid deposition in Tg2576 mice
Spatial relationship between synapse loss and β-amyloid deposition in Tg2576 mice
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DOI：
10.1002/cne.21176
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发表时间：
2007-01-10
影响因子：
2.5
通讯作者：
Csernansky, John G.
中科院分区：
文献类型：
--
作者：
Dong, Hongxin;Martin, Maureen V.;Csernansky, John G.
虽然有证据表明β-淀粉样蛋白损害突触功能，β-淀粉样蛋白和突触损失之间的关系还没有得到很好的理解。在这项研究中，我们评估了突触密度内海马和内嗅皮质的Tg 2576小鼠在6-18个月的年龄，使用体视学方法在光镜和电镜水平。在光学显微镜下，我们没有发现在任何脑区选择的突触体蛋白阳性终扣的密度整体下降，但终扣密度显着降低200 μ m内的致密β-淀粉样蛋白斑块的齿状回和层II和III的内嗅皮质在15-18个月的年龄Tg 2576小鼠的外分子层。在电子显微镜下，我们发现在6-9和15-18个月大的齿状回的外分子层的突触密度的整体下降，并在层II和III的内嗅皮层在15-18个月大的Tg 2576小鼠。然而，我们没有发现整体的变化，突触密度在辐射层的CA 1子域。此外，在前两个大脑区域中，我们发现较低的突触密度和更接近β-淀粉样蛋白斑块之间存在相关性。这些结果提供了第一个定量的形态学证据，在超微结构水平的β-淀粉样蛋白斑块和突触损失之间的空间关系在海马和内嗅皮层的Tg 2576小鼠。
Although there is evidence that beta-amyloid impairs synaptic function, the relationship between beta-amyloid and synapse loss is not well understood. In this study we assessed synapse density within the hippocampus and the entorhinal cortex of Tg2576 mice at 6-18 months of age using stereological methods at both the light and electron microscope levels. Under light microscopy we failed to find overall decreases in the density of synaptophysin-positive boutons in any brain areas selected, but bouton density was significantly decreased within 200 mu m of compact beta-amyloid plaques in the outer molecular layer of the dentate gyrus and Layers II and III of the entorhinal cortex at 15-18 months of age in Tg 2576 mice. Under electron microscopy, we found overall decreases in synapse density in the outer molecular layer of the dentate gyrus at both 6-9 and 15-18 months of age, and in Layers Il and III of the entorhinal cortex at 15-18 months of age in Tg 2576 mice. However, we did not find overall changes in synapse density in the stratum radiatum of the CA1 subfield. Furthermore, in the two former brain areas we found a correlation between lower synapse density and greater proximity to beta-amyloid plaques. These results provide the first quantitative morphological evidence at the ultrastructure level of a spatial relationship between beta-amyloid plaques and synapse loss within the hippocampus and the entorhinal cortex of Tg2576 mice.