Login Register Cart 0
Generic placeholder image

当代阿耳茨海默病研究

Editor-in-Chief

ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe Translate in English
Research Article

锌螯合剂HQ-O对APP-PS1小鼠和患有阿尔茨海默病的人类组织切片中淀粉样斑块的高对比度和高分辨率标记：实际和理论上的考虑

卷 16, 期 7, 2019

页: [577 - 586] 页: 10

弟呕挨: 10.2174/1567205016666190725155038

open access plus

摘要

背景：在许多有关阿尔茨海默氏病的研究中，已经采用了各种方法来定位淀粉样斑块。 这些斑块中的大多数被认为是由于斑块对聚集的Aβ的亲和力而标记了斑块。 然而，已知斑块包含许多其他成分，包括诸如锌的多价金属。 目的：研究是否可以在患病的大脑的实质和血管淀粉样斑块中定位锌的存在。 为此，研究了一种新型荧光锌螯合剂HQO，及其在淀粉样斑块高对比度和高分辨组织学定位中的作用机制，并对其染色进行了优化。 方法：开发了一种新型的锌螯合剂HQ-O，用于在淀粉样斑块中定位锌。 组织学包括将组织切片在HQ-O的稀水溶液中孵育。描述了其与多种其他荧光方法的兼容性。 结果：所有淀粉样蛋白斑块均被细微染色，在蓝光激发下呈亮绿色。 实质斑块的染色与抗Aβ抗体染色后的染色密切相关，但是，HQ-O有时还会标记血管内的其他球状结构。原位机理研究表明，只有在锌存在下合成Aβx-42聚集时，HQ-O才能观察到荧光斑块状结构。 结论：锌与所有淀粉样蛋白斑块紧密结合，使用新型荧光锌螯合剂HQ-O的组织学定位证明了锌的存在。 另外，示踪剂由于其高锌含量也能够标记血管内白细胞。

关键词: 淀粉样斑块，阿尔茨海默病，锌螯合剂，脑病理学，Aβ，淀粉酶。

Next »
[1]
Puchtler H, Sweat F. Congo red as a stain for fluorescence microscopy of amyloid. J Histochem Cytochem 13(8): 693-4. (1965)
[http://dx.doi.org/10.1177/13.8.693] [PMID: 4160077]
[2]
Kelényi G. Thioflavin S fluorescent and Congo red anisotropic stainings in the histologic demonstration of amyloid. Acta Neuropathol 7(4): 336-48. (1967)
[http://dx.doi.org/10.1007/BF00688089] [PMID: 4166287]
[3]
Schmued L, Raymick J, Tolleson W, Sarkar S, Bell-Cohn A. Introducing Amylo-Glo, a novel histochemical trracer especially suited for multiple labeling and large scale quantification studies. J Neurosci Methods 30(209): 120-6. (2012)
[http://dx.doi.org/10.1016/j.jneumeth.2012.05.019] [PMID: 22705750]
[4]
Sato K, Higuchi M, Iwata N, Saido TC, Sasamoto K. Fluoro-substituted and 13C-labeled styrylbenzene derivatives for detecting brain amyloid plaques. Eur J Med Chem 39(7): 573-8. (2004)
[http://dx.doi.org/10.1016/j.ejmech.2004.02.013] [PMID: 15236837]
[5]
Lee JY, Mook-Jung I, Koh JY. Histochemically reactive zinc in plaques of the Swedish mutant beta-amyloid precursor protein transgenic mice. J Neurosci 19(11): RC10. (1999)
[http://dx.doi.org/10.1523/JNEUROSCI.19-11-j0002.1999] [PMID: 10341271]
[6]
Falangola MF, Lee SP, Nixon RA, Duff K, Helpern JA. Histological co-localization of iron in Abeta plaques of PS/APP transgenic mice. Neurochem Res 30(2): 201-5. (2005)
[http://dx.doi.org/10.1007/s11064-004-2442-x] [PMID: 15895823]
[7]
Bourassa MW, Leskovjan AC, Tappero RV, Farquhar ER, Colton CA, Van Nostrand WE, et al. Elevated copper in the amyloid plaques and iron in the cortex are observed in mouse models of Alzheimer’s disease that exhibit neurodegeneration. Biomed Spectrosc Imaging 2(2): 129-39. (2013)
[PMID: 24926425]
[8]
Prachayasittikul V, Prachayasittikul S, Ruchirawat S, Prachayasittikul V. 8-Hydroxyquinolines: a review of their metal chelating properties and medicinal applications. Drug Des Devel Ther 7: 1157-78. (2013)
[http://dx.doi.org/10.2147/DDDT.S49763] [PMID: 24115839]
[9]
Smith GL, Jenkins RA, Gough JF. A fluorescent method for the detection and localization of zinc in human granulocytes. J Histochem Cytochem 17(11): 749-50. (1969)
[http://dx.doi.org/10.1177/17.11.749] [PMID: 5386301]
[10]
Sternberg SS, Cronin A, Philips FS. Histochemical demonstration of zinc in the dorsolateral prostate of the rat: studies with oxine and dithizone. Am J Pathol 47: 325-37. (1965)
[PMID: 14335773]
[11]
Iwatsubo T, Odaka A, Suzuki N, Mizusawa H, Nukina N, Ihara Y. Visualization of A beta 42(43) and A beta 40 in senile plaques with end-specific A beta monoclonals: evidence that an initially deposited species is A beta 42(43). Neuron 13(1): 45-53. (1994)
[http://dx.doi.org/10.1016/0896-6273(94)90458-8] [PMID: 8043280]
[12]
Cherny RA, Barnham KJ, Lynch T, Volitakis I, Li QX, McLean CA, et al. Chelation and intercalation: complementary properties in a compound for the treatment of Alzheimer’s disease. J Struct Biol 130(2-3): 209-16. (2000)
[http://dx.doi.org/10.1006/jsbi.2000.4285] [PMID: 10940226]
[13]
James SA, Churches QI, de Jonge MD, Birchall IE, Streltsov V, McColl G, et al. Iron, Copper, and Zinc Concentration in Aβ plaques in the app/ps1 mouse model of Alzheimer’s disease correlates with metal levels in the surrounding neuropil. ACS Chem Neurosci 8(3): 629-37. (2017)
[http://dx.doi.org/10.1021/acschemneuro.6b00362] [PMID: 27958708]
[14]
Bush AI, Pettingell WH Jr, de Paradis M, Tanzi RE, Wasco W. The amyloid beta-protein precursor and its mammalian homologues. Evidence for a zinc-modulated heparin-binding superfamily. J Biol Chem 269(43): 26618-21. (1994)
[PMID: 7929392]
[15]
Cherny RA, Atwood CS, Xilinas ME, Gray DN, Jones WD, McLean CA, et al. Treatment with a copper-zinc chelator markedly and rapidly inhibits beta-amyloid accumulation in Alzheimer’s disease transgenic mice. Neuron 30(3): 665-76. (2001)
[http://dx.doi.org/10.1016/S0896-6273(01)00317-8] [PMID: 11430801]
[16]
Zhang YH, Raymick J, Sarkar S, Lahiri DK, Ray B, Holtzman D, et al. Efficacy and toxicity of clioquinol treatment and A-beta42 inoculation in the APP/PSI mouse model of Alzheimer’s disease. Curr Alzheimer Res 10(5): 494-506. (2013)
[http://dx.doi.org/10.2174/1567205011310050005] [PMID: 23627708]
[17]
Tsubaki T, Honma Y, Hoshi M. Neurological syndrome associated with clioquinol. Lancet 1(7701): 696-7. (1971)
[http://dx.doi.org/10.1016/S0140-6736(71)92699-7] [PMID: 4101631]
[18]
Tyszka-Czochara M, Grzywacz A, Gdula-Argasińska J, Librowski T, Wiliński B, Opoka W. The role of zinc in the pathogenesis and treatment of central nervous system (CNS) diseases. Implications of zinc homeostasis for proper CNS function. Acta Pol Pharm 71(3): 369-77. (2014)
[PMID: 25265815]

Rights & Permissions Print Cite
Article Metrics
39
7
© 2024 Bentham Science Publishers | Privacy Policy