Iron storage within dopamine neurovesicles revealed by chemical nano-imaging.
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 substantia 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.
Ortega
Richard
R
Cellular Chemical Imaging and Speciation Group, Chimie Nucléaire Analytique Bioenvironnementale, Centre National de la Recherche Scientifique, Université Bordeaux 1, Gradignan, France. ortega@cenbg.in2p3.fr
Cloetens
Peter
P
Devès
Guillaume
G
Carmona
Asunción
A
Bohic
Sylvain
S
D000818:Animals; D022162:Cytoplasmic Vesicles / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D005453:Fluorescence; D007501:Iron / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D036103:Nanotechnology / Q000379:methods; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016716:PC12 Cells; D011188:Potassium / Q000378:metabolism; D051381:Rats; D013052:Spectrometry, X-Ray Emission / Q000379:methods; D014446:Tyrosine 3-Monooxygenase / Q000037:antagonists & inhibitors; D015032:Zinc / Q000378:metabolism; D019805:alpha-Methyltyrosine / Q000494:pharmacology
D019805:alpha-Methyltyrosine; D007501:Iron; D014446:Tyrosine 3-Monooxygenase; D015032:Zinc; D011188:Potassium; D004298:Dopamine