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Analysis of neuronal iron deposits in Parkinson's disease brain tissue by synchrotron x-ray spectromicroscopy
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Brooks, Jake, Everett, James, Lermyte, Frederik, Tjhin, Vindy Tjendana, Sadler, Peter J., Telling, Neil D. and Collingwood, Joanna F. (2020) Analysis of neuronal iron deposits in Parkinson's disease brain tissue by synchrotron x-ray spectromicroscopy. Journal of Trace Elements in Medicine and Biology, 62 . 126555. doi:10.1016/j.jtemb.2020.126555 ISSN 0946-672X.
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Official URL: http://dx.doi.org/10.1016/j.jtemb.2020.126555
Abstract
Background
Neuromelanin-pigmented neurons, which are highly susceptible to neurodegeneration in the Parkinson’s disease substantia nigra, harbour elevated iron levels in the diseased state. Whilst it is widely believed that neuronal iron is stored in an inert, ferric form, perturbations to normal metal homeostasis could potentially generate more reactive forms of iron capable of stimulating toxicity and cell death. However, non-disruptive analysis of brain metals is inherently challenging, since use of stains or chemical fixatives, for example, can significantly influence metal ion distributions and/or concentrations in tissues.
Aims
The aim of this study was to apply synchrotron soft x-ray spectromicroscopy to the characterisation of iron deposits and their local environment within neuromelanin-containing neurons of Parkinson’s disease substantia nigra.
Methods
Soft x-ray spectromicroscopy was applied in the form of Scanning Transmission X-ray Microscopy (STXM) to analyse resin-embedded tissue, without requirement for chemically disruptive processing or staining. Measurements were performed at the oxygen and iron K-edges in order to characterise both organic and inorganic components of anatomical tissue using a single label-free method.
Results
STXM revealed evidence for mixed oxidation states of neuronal iron deposits associated with neuromelanin clusters in Parkinson’s disease substantia nigra. The excellent sensitivity, specificity and spatial resolution of these STXM measurements showed that the iron oxidation state varies across sub-micron length scales.
Conclusions
The label-free STXM approach is highly suited to characterising the distributions of both inorganic and organic components of anatomical tissue, and provides a proof-of-concept for investigating trace metal speciation within Parkinson’s disease neuromelanin-containing neurons.
| Item Type: | Journal Article | |||||||||||||||
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| Subjects: | Q Science > QC Physics R Medicine > RB Pathology R Medicine > RC Internal medicine |
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| Divisions: | Faculty of Science, Engineering and Medicine > Science > Chemistry Faculty of Science, Engineering and Medicine > Engineering > Engineering |
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| Library of Congress Subject Headings (LCSH): | Parkinson's disease, Brain -- Diseases , Grenz rays , Oxidative stress, Nervous system -- Degeneration -- Molecular aspects | |||||||||||||||
| Journal or Publication Title: | Journal of Trace Elements in Medicine and Biology | |||||||||||||||
| Publisher: | Elsevier | |||||||||||||||
| ISSN: | 0946-672X | |||||||||||||||
| Official Date: | December 2020 | |||||||||||||||
| Dates: |
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| Volume: | 62 | |||||||||||||||
| Article Number: | 126555 | |||||||||||||||
| DOI: | 10.1016/j.jtemb.2020.126555 | |||||||||||||||
| Status: | Peer Reviewed | |||||||||||||||
| Publication Status: | Published | |||||||||||||||
| Access rights to Published version: | Restricted or Subscription Access | |||||||||||||||
| Date of first compliant deposit: | 8 June 2020 | |||||||||||||||
| Date of first compliant Open Access: | 9 June 2020 | |||||||||||||||
| RIOXX Funder/Project Grant: |
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