Intracellular Chemical Imaging of the Developmental Phases of Human Neuromelanin Using Synchrotron X-ray Microspectroscopy
Intracellular Chemical Imaging of the Developmental Phases of Human Neuromelanin Using Synchrotron X-ray Microspectroscopy
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DOI：
10.1021/ac801817k
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发表时间：
2008-12-15
影响因子：
7.4
通讯作者：
Double, Kay
中科院分区：
文献类型：
--
作者：
Bohic, Sylvain;Murphy, Karen;Double, Kay
用同步辐射化学X射线显微镜观察了福尔马林固定和石蜡包埋的人黑质神经元中神经黑色素（NM）的微化学环境。NM相关元素的浓度增加，在发育中的大脑，最高水平的大多数元素被发现在成熟的大脑，但不同元素的积累的时间模式各不相同。高空间分辨率的调查，使用独特的硬X射线纳米探针，揭示了富铁的微区与其他元素的颜料内共定位。这些微区代表了第一个可视化的结构调节NM的金属结合特性，并支持NM在色素神经元中的功能重要元素的调节中的生理作用。我们的研究结果表明，当地的化学环境中的铁NM是类似的铁蛋白中发现，并指出可能的作用，铁NM生物合成。细胞内形态的硫包含在NM显示存在还原硫化合物和各种形式的氧化硫化合物，这是以前没有报道。此外，一个显着增加磺酸盐在NM在成熟的大脑表明，在体内代谢的色素通过尚未确定的途径发生。目前的数据增加了我们对NM在人脑中的发展和调节的理解。
The microchemical environment of neuromelanin (NM) in whole neurons from formalin fixed and paraffin embedded human substantial nigra sections were characterized using synchrotron chemical X-ray microscopy. Concentrations of NM-associated elements increased in the developing brain; the highest levels of most elements were found in the mature brain but the temporal pattern of the accumulation of different elements varied. High spatial resolution investigations, using a unique hard X-ray nanoprobe, revealed iron-rich microdomains colocalized with other elements within the pigment. These microdomains represent the first visualization of a structure regulating the metal-binding properties of NM and supporting a physiological role for NM in the regulation of functionally important elements in pigmented neurons. Our results demonstrate that the local chemical environment of iron in NM is similar to that found in ferritin and points to a possible role of iron in NM biosynthesis. Intracellular speciation of sulfur contained in NM revealed the presence of reduced sulfur compounds and various forms of oxidized sulfur compounds which have not previously been reported. Further, a significant increase in sulfonate in NM in the mature brain suggests that in vivo metabolism of the pigment via an as yet unidentified pathway occurs. The current data add to our understanding of the development and regulation of NM in the human brain.