Iron storage within dopamine neurovesicles revealed by chemical nano-imaging.
Iron storage within dopamine neurovesicles revealed by chemical nano-imaging.
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DOI：
10.1371/journal.pone.0000925
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发表时间：
2007-09-26
期刊：
影响因子：
--
通讯作者：
Edwards, Jonathan
中科院分区：
文献类型：
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作者：
Edwards, Jonathan
金属离子的稳态改变被怀疑在神经变性中起关键作用。然而，缺乏足够的空间分辨率的分析技术，阻止了金属在神经元中分布的调查。一个原始的实验装置开发，以执行化学元素成像与90 nm的空间分辨率，使用同步加速器为基础的X射线荧光。这种独特的空间分辨率与高亮度相结合，使亚细胞区室中的化学元素成像成为可能。我们研究了铁在产生多巴胺的神经元中的分布，因为人们怀疑铁-多巴胺化合物会形成，但从未在细胞中观察到。这项研究表明，铁积累到多巴胺神经囊泡。此外，多巴胺合成的抑制导致铁的囊泡储存减少。这些结果表明多巴胺在正常多巴胺产生细胞内的铁缓冲中的新生理作用。该系统可能在帕金森氏病中存在故障，帕金森氏病的特征在于黑质中的铁水平增加以及由于囊泡运输的破坏而导致的多巴胺储存受损。高活性多巴胺-铁复合物在神经囊泡外的重新分布将导致多巴胺能神经元的死亡增加。
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.