科学家一直怀疑铁沉积会导致神经退化疾病－例如帕金森氏症等，但由于技术方面的缺陷，铁对于神经的影响从未被观察到过。而最近，来自法国Bordeaux大学CNRS、西班牙Sevilla大学、INSERM Grenoble神经科学研究所和ESRF的科学家研究了体外产生多巴胺的神经细胞中铁的分布。
多巴胺是哺乳动物大脑神经细胞间的化学信使。由于多巴胺和铁能形成稳定复合物，来自Bordeaux的细胞化学成像小组的Richard Ortega认为能通过缓冲多巴胺神经元中的铁产生一种保护作用，而在帕金森氏症中该系统可能存在问题。
为了测试以上假设，小组利用了欧洲同步加速辐射器发明的最新纳米探针成像装置，来研究细胞中的元素分布。90纳米的分辨率使得科学家可以观察神经传递素内的元素分布。纳米探针通过聚焦强X射线激发样品，然后收集发射出的特征荧光。这能帮助区分一点上的不同微量元素，然后通过点扫描得到细胞完整的多元素图像。
小组发现铁储存在神经细胞中的多巴胺小泡中。这是铁-多巴胺在小泡中共存的首个证据。科学家同时发现当多巴胺的制造发生困难时，小泡中的铁也快速降低。这种多巴胺小泡在铁储存中的新作用对于了解帕金森氏症等疾病的分子机制非常重要。发生神经异常时，多巴胺小泡存储被破坏，最终将增加铁-多巴胺复合物在神经中的毒性。结果发表在9月26日的PLoS ONE上。
除了研究神经退化疾病外，同步纳米成像装置还能用于其它需要分析铁亚细胞分布的领域，例如：金属毒物学、化学致癌、无机化合物的细胞药理学等。这也是科学家为何将结果公布于PLoS ONE这样的开放性刊物的重要原因。ESRF的负责人Peter Cloetens说：“我们希望不同的研究组织知道这种仪器，最好的方法是让每个人都能知道研究结果。” *(教育部科技发展中心)
原文链接：http://www.physorg.com/news111245716.html
原始出处：
PLoS ONE
Received: February 19, 2007; Accepted: August 8, 2007; Published: September 26, 2007
Iron Storage within Dopamine Neurovesicles Revealed by Chemical Nano-Imaging
Richard Ortega1*, Peter Cloetens2, Guillaume Devès1, Asunción Carmona3, Sylvain Bohic4
1 Cellular Chemical Imaging and Speciation Group, Chimie Nucléaire Analytique Bioenvironnementale, Centre National de la Recherche Scientifique, Université Bordeaux 1, Gradignan, France, 2 X-Ray Imaging Group, European Synchrotron Radiation Facility, Grenoble, France, 3 Centro Nacional de Aceleradores, Universidad de Sevilla, Sevilla, Spain, 4 INSERM U-836, Equipe Rayonnement Synchrotron et Recherche Médicale, Grenoble Institut des Neurosciences, European Synchrotron Radiation Facility, Grenoble, France
Abstract
Altered homeostasis of metal ions is suspected to play a critical role in neurodegeneration. However, the lack of analytical technique with sufficient spatial resolution prevents the investigation of metals distribution in neurons. An original experimental setup was developed to perform chemical element imaging with a 90 nm spatial resolution using synchrotron-based X-ray fluorescence. This unique spatial resolution, combined to a high brightness, enables chemical element imaging in subcellular compartments. We investigated the distribution of iron in dopamine producing neurons because iron-dopamine compounds are suspected to be formed but have yet never been observed in cells. The study shows that iron accumulates into dopamine neurovesicles. In addition, the inhibition of dopamine synthesis results in a decreased vesicular storage of iron. These results indicate a new physiological role for dopamine in iron buffering within normal dopamine producing cells. This system could be at fault in Parkinson's disease which is characterized by an increased level of iron in the substancia nigra pars compacta and an impaired storage of dopamine due to the disruption of vesicular trafficking. The re-distribution of highly reactive dopamine-iron complexes outside neurovesicles would result in an enhanced death of dopaminergic neurons.
