Selective, quantitative measurement of releasable synaptic zinc in human autopsy hippocampal brain tissue from Alzheimer's disease patients
Selective, quantitative measurement of releasable synaptic zinc in human autopsy hippocampal brain tissue from Alzheimer's disease patients
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DOI：
10.1016/j.jneumeth.2011.09.008
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发表时间：
2012-01-15
影响因子：
3
通讯作者：
Taglialatela, Giulio
中科院分区：
文献类型：
--
作者：
Bjorklund, Nicole L.;Sadagoparamanujam, V. -M.;Taglialatela, Giulio
中枢神经系统锌稳态异常已被报道在阿尔茨海默病（AD）。然而，有相互矛盾的报告，描述锌浓度增加或减少，在大脑中的AD患者。这种差异可能是由于检查的大脑区域，锌检测方法和/或组织成分的差异。此外，检测和测量尸体解剖组织中的可释放锌池是困难的，并且通常是不可靠的。获得对这种可释放的锌库的充分评估在AD研究中具有特别重要的意义，因为锌可以与毒性淀粉样蛋白β寡聚体协调并使其稳定，这被认为在AD神经病理学中起关键作用。此外，释放到突触间隙中的锌可以与突触后神经元相互作用，导致信号传导改变和突触功能障碍，这是AD中公认的事件。这里提出的方法结合了两种方法，生化分馏和原子吸收分光光度法，允许，除了细胞外锌浓度，锌的可靠和定量测量，具体定位在突触囊泡，其中包含大部分的神经元可释放的锌。使用这种方法，我们发现，突触囊泡锌浓度增加，在AD的年龄匹配的对照组相比，可释放的锌增加匹配的细胞外空间中的锌浓度增加。(C)2011 Elsevier B. V.保留所有权利。
Aberrant central nervous system zinc homeostasis has been reported in Alzheimer's disease (AD). However, there are conflicting reports describing zinc concentration either increased or decreased in the brain of AD patients. Such discrepancies may be due to differences in the brain area examined, zinc detection method, and/or tissue composition. Furthermore, detection and measurement of the releasable zinc pool in autopsy tissue is difficult and usually unreliable. Obtaining an adequate assessment of this releasable zinc pool is of particular significance in AD research in that zinc can coordinate with and stabilize toxic amyloid beta oligomers, which are believed to play a key role in AD neuropathology. In addition, zinc released into the synaptic cleft can interact with the postsynaptic neurons causing altered signaling and synaptic dysfunction, which is a well established event in AD. The method presented here combines two approaches, biochemical fractionation and atomic absorption spectrophotometry, to allow, in addition to extracellular zinc concentration, the reliable and quantitative measurement of zinc specifically localized in synaptic vesicles, which contain the majority of the neuronal releasable zinc. Using this methodology, we found that synaptic vesicle zinc concentrations were increased in AD hippocampi compared to age-matched controls and that this increase in releasable zinc matched increased concentration of zinc in the extracellular space. (C) 2011 Elsevier B.V. All rights reserved.