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Label-free nanoimaging of neuromelanin in the brain by soft X-ray spectromicroscopy

DOI: 10.1002/anie.202000239 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) , Samya Banerjee (University of Warwick) , Peter B. O’connor (University of Warwick) , Christopher M. Morris (Newcastle University) , Peter J. Sadler (University of Warwick) , Neil D. Telling (Keele University) , Joanna F. Collingwood (Warwick University)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Angewandte Chemie International Edition

State: Published (Approved)
Published: March 2020
Diamond Proposal Number(s): 15230 , 15854 , 20809 , 24526 , 24531

Abstract: A hallmark of Parkinson’s disease is the death of neuromelanin‐pigmented neurons, but the role of neuromelanin is unclear. Lack of a neuromelanin‐specific marker was highlighted over 30 years ago, yet in‐situ characterization of neuromelanin remains dependent on detectable pigmentation, rather than direct quantification of neuromelanin. We show that direct, label‐free nanoscale visualization of neuromelanin and associated metal ions in human brain tissue can be achieved using synchrotron Scanning Transmission X‐ray Microscopy (STXM), via a characteristic feature in the neuromelanin x‐ray absorption spectrum at 287.4 eV that is also present in iron‐free and iron‐laden synthetic neuromelanin. This is confirmed in consecutive brain sections by correlating STXM neuromelanin imaging with silver nitrate‐stained neuromelanin. Analysis suggests that the 1s ‐ σ* (C‐S) transition in benzothiazine groups accounts for this feature. This advance in visualizing neuromelanin illustrates the wider potential of STXM as a label‐free spectromicroscopy technique applicable to both organic and inorganic materials.

Journal Keywords: iron; Neuromelanin; Parkinson's disease; Synchrotron imaging; X-ray absorption spectroscopy

Subject Areas: Biology and Bio-materials, Technique Development

Instruments: I08-Scanning X-ray Microscopy beamline (SXM) , I14-Hard X-ray Nanoprobe