Histochemically Reactive Zinc in Plaques of the Swedish Mutant β-Amyloid Precursor Protein Transgenic Mice
Histochemically Reactive Zinc in Plaques of the Swedish Mutant β-Amyloid Precursor Protein Transgenic Mice
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DOI：
10.1523/jneurosci.19-11-j0002.1999
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发表时间：
1999-06-01
影响因子：
5.3
通讯作者：
Koh, JY
中科院分区：
文献类型：
--
作者：
Lee, JY;Mook-Jung, I;Koh, JY
内源性金属如锌可能有助于β-淀粉样蛋白（A β）聚集，从而形成斑块。在本研究中，我们研究了四个瑞典突变淀粉样前体蛋白（APP）转基因小鼠在12个月大的组织化学反应锌的斑块。在这里，我们报告说，所有的刚果红（+）成熟斑块含有螯合锌，证明了与锌特异性荧光染料6-甲氧基-8-喹啉基-对甲苯磺酰胺（TSQ）染色。另一方面，刚果红（-）类胡萝卜素A β沉积物未被TSQ染色。有趣的是，尽管小脑含有与大脑皮层相似程度的类胶质A β沉积，但完全没有刚果红或TSQ染色的成熟斑块。虽然锌从斑块中只能缓慢和部分地被一种特殊的锌去除剂双硫腙去除，但用肝素酶-III处理脑切片，可以降解硫酸乙酰肝素蛋白聚糖（HSPG），另一种主要的斑块成分，大大加快了双硫腙对锌的去除。本研究表明，在斑块中存在组织化学反应性锌，而不是类磷脂A β沉积，瑞典突变型APP转基因小鼠。由于小脑突触囊泡锌缺乏，类胶质A β沉积物不能形成嗜酸性斑，因此突触锌可能是斑形成的必要因素。在将锌保持在斑块内时，除了A β之外，HSPG可能也有贡献。
Endogenous metals such as zinc may contribute to beta-amyloid (A beta) aggregation and hence the plaque formation. In the present study, we examined brains of four Swedish mutant amyloid precursor protein (APP) transgenic mice at 12 months of age for histochemically reactive zinc in the plaques. Here, we report that all the Congo red (+) mature plaques contained chelatable zinc, as demonstrated by staining with the zinc-specific fluorescent dye 6-methoxy-8-quinolyl-para-toluenesulfonamide (TSQ). On the other hand, Congo red (-) preamyloid A beta deposits were not stained with TSQ. Interestingly, although cerebellum contained similar degree of preamyloid A beta deposits as cerebral cortex, it was completely devoid of Congo red- or TSQ-stained mature plaques. Although zinc from plaques was only slowly and partially removed by a specific zinc remover, dithizone, treatment of brain sections with heparinase-III, which degrades heparan sulfate proteoglycan (HSPG), another major constituent of plaques, greatly fastened the zinc removal with dithizone.The present study has demonstrated the presence of histochemically reactive zinc in plaques, but not preamyloid A beta deposits, of the Swedish mutant APP transgenic mice. Because preamyloid A beta deposits fail to develop into congophilic plaques in cerebellum where synaptic vesicle zinc is deficient, the synaptic zinc may be a necessary element in the plaque formation. In holding zinc inside plaques, HSPG may contribute in addition to A beta.