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Intracellular Chemical Imaging of the Developmental Phases of Human Neuromelanin Using Synchrotron X-ray Microspectroscopy.

Abstract : The microchemical environment of neuromelanin (NM) in whole neurons from formalin fixed and paraffin embedded human substantia 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.
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Submitted on : Thursday, August 20, 2009 - 4:47:36 PM
Last modification on : Thursday, June 9, 2022 - 8:20:04 AM

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Sylvain Bohic, Karen Murphy, Werner Paulus, Peter Cloetens, Murielle Salomé, et al.. Intracellular Chemical Imaging of the Developmental Phases of Human Neuromelanin Using Synchrotron X-ray Microspectroscopy.. Analytical Chemistry, American Chemical Society, 2008, epub ahead of print. ⟨10.1021/ac801817k⟩. ⟨inserm-00410454⟩



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