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Updated: May 8, 2026
Functional Neuroimaging Using Ultrasonic Blood-brain Barrier Disruption and Manganese-enhanced MRI
Published on: July 12, 2012
X-ray fluorescence imaging of the hippocampal formation after manganese exposure
Gregory Robison1, Taisiya Zakharova, Sherleen Fu
1Purdue University, Department of Physics, 525 Northwestern Avenue, West Lafayette, IN 47907, USA. ypushkar@purdue.edu.
Abstract:
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.
Insights
Manganese (Mn) intoxication causes neurological issues. This study used X-ray fluorescence imaging to show Mn accumulates in specific brain areas, suggesting links with iron and zinc transport mechanisms.
Area of Science:
- Neuroscience
- Toxicology
- Biochemistry
Background:
- Manganese intoxication mimics Parkinson's disease symptoms.
- High manganese accumulation occurs in the hippocampal formation (HPCf).
- Current imaging methods lack metal quantification capabilities.
Purpose of the Study:
- To quantitatively measure manganese distribution in the HPCf.
- To compare manganese distribution with other metals.
- To elucidate mechanisms of manganese transport and storage in the brain.
Main Methods:
- Utilized X-ray fluorescence imaging on a rodent model of chronic manganese exposure.
- Quantified manganese distribution within the hippocampal formation.
- Correlated manganese distribution with iron and zinc concentrations.
Main Results:
- Significant increases in average manganese concentrations were observed across all analyzed HPCf areas.
- The dentate gyrus (DG) and CA3 layer showed the highest manganese accumulation.
- Spatial correlations between manganese-zinc and manganese-iron concentrations were identified, suggesting distinct transport/storage mechanisms.
Conclusions:
- Manganese accumulation in the HPCf is linked to iron and zinc, indicating at least two transport/storage pathways.
- Manganese-zinc correlation at cellular levels suggests involvement of zinc transport mechanisms in manganese accumulation.
- Findings provide insights into the neurotoxic mechanisms of manganese exposure.
