Issue 11, 2013

X-ray fluorescence imaging of the hippocampal formation after manganese exposure


Manganese (Mn) intoxication results in neurological conditions similar, but not identical, to idiopathic Parkinson's disease. While the mechanism(s) by which Mn exposure leads to neurotoxic effects remains unclear, studies by magnetic resonance imaging demonstrate a high Mn accumulation in the hippocampal formation (HPCf) of the brain. Metal quantification using this method is not possible. Using X-ray fluorescence imaging, we measured the distribution of Mn in the HPCf for a rodent model of chronic Mn exposure and quantitatively compared it with distributions of other biologically relevant metals. We found considerable increases in average Mn concentrations in all analyzed areas and we identified the dentate gyrus (DG) and the cornus ammonis 3 (CA3) layer as areas accumulating the highest Mn content (∼1.2 μg Mn per g tissue). The DG is significantly enriched with iron (Fe), while the CA3 layer has high zinc (Zn) content. Additionally, significant spatial correlations were found for Mn–Zn concentrations across the HPCf substructures and for Mn–Fe concentrations in the DG. Combined results support that at least two mechanisms may be responsible for Mn transport and/or storage in the brain, associated with either Fe or Zn. Subcellular resolution images of metal distribution in cells of the CA3 show diffuse Mn distributions consistent with Mn localization in both the cytoplasm and nucleus. Mn was not increased in localized intracellular Fe or copper accumulations. A consistent Mn–Zn correlation both at the tissue (40 μm × 40 μm) and cellular (0.3 μm × 0.3 μm) levels suggests that a Zn transport/storage mechanism in the HPCf is likely associated with Mn accumulation.

Graphical abstract: X-ray fluorescence imaging of the hippocampal formation after manganese exposure

Supplementary files

Article information

Article type
29 Apr 2013
01 Aug 2013
First published
01 Aug 2013

Metallomics, 2013,5, 1554-1565