Environmental exposure to neurotoxic metals such as manganese could be one of the risk factors causing Parkinson’s disease. Organometallic manganese compounds are used as pesticides (Maneb), or as additives in unleaded gasoline (MMT).
Using micro-SXRF methods (Synchrotron X -Ray Fluorescence) and micro-XAS (X -ray Absorption Spectroscopy) at the ESRF (European Synchrotron Radiation Facility), we highlighted the accumulation of manganese in the Golgi apparatus of dopaminergic cells (see figure).
This result, completely new, tells us about the detoxification mechanisms of this element and the possible link to Parkinson’s disease. Disruption of vesicular trafficking by alteration and fragmentation of the Golgi apparatus could explain the neurotoxic effects of Mn, especially on the critical dopaminergic system affected by neurodegeneration.
In addition we have shown that whatever the nature of environmental Mn compounds (inorganic, organometallic), the mechanism of toxicity is the same and involves an interaction of Mn2+ ions with the Golgi apparatus. Toxicity is proportional to the solubility of the compounds, as shown by speciation, joining the toxicity paradigm vs solubility described for cobalt oxide.
Figure. Micro-SXRF imaging and micro-XAS spectroscopy of dopaminergic neurons exposed in vitro to Mn showing accumulation in the Golgi apparatus and speciation as Mn2+. Data obtained at the ESRF ID21 beamline. Scale bar : 10 µm.
compounds accumulate as Mn(II) within the Golgi
apparatus of dopamine cells : relationship between speciation,
subcellular distribution, and cytotoxicity
Carmona A., Roudeau S., Perrin L., Veronesi G., Ortega R. (2014), Metallomics, 6, 822-832. [pubmed] [link]
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