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Analysis of neuronal iron deposits in Parkinson's disease brain tissue by synchrotron x-ray spectromicroscopy

DOI: 10.1016/j.jtemb.2020.126555 DOI Help

Authors: Jake Brooks (University of Warwick) , James Everett (University of Warwick; Keele University) , Frederik Lermyte (University of Warwick) , Vindy Tjendana Tjhin (University of Warwick) , Peter J. Sadler (University of Warwick) , Neil Telling (Keele University) , Joanna F. Collingwood (Warwick University)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Journal Of Trace Elements In Medicine And Biology

State: Published (Approved)
Published: May 2020
Diamond Proposal Number(s): 15230

Open Access Open Access

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.

Journal Keywords: Parkinson’s disease; Iron; Oxidation state; Soft x-ray; Spectromicroscopy; Synchrotron

Subject Areas: Biology and Bio-materials, Technique Development

Instruments: I08-Scanning X-ray Microscopy beamline (SXM)

Other Facilities: Beamline 11.0.2 at Advanced Light Source