Label-Free Nanoimaging of Neuromelanin in the Brain by Soft X-ray Spectromicroscopy

Overview

Journal Angew Chem Int Ed Engl

Specialty Chemistry

Date 2020 Apr 1

PMID 32227670

Citations 11

Authors

Jake Brooks

James Everett

Frederik Lermyte

Vindy Tjendana Tjhin

Samya Banerjee

Peter B OConnor

Christopher M Morris

Peter J Sadler

Neil D Telling

Joanna F Collingwood

Affiliations

Soon will be listed here.

Abstract

A hallmark of Parkinson's disease is the death of neuromelanin-pigmented neurons, but the role of neuromelanin is unclear. The 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), through 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 method illustrates the wider potential of STXM as a label-free spectromicroscopy technique applicable to both organic and inorganic materials.

Citing Articles

On the origin of metal species in the human brain: a perspective on key physicochemical properties.

Brooks J, Everett J, Sadler P, Telling N, Collingwood J Metallomics. 2025; 17(3).

PMID: 39924175 PMC: 11890113. DOI: 10.1093/mtomcs/mfaf004.

Soft X-ray spectromicroscopy of human fibroblasts with impaired sialin function.

Mansikkala T, Kangas S, Miinalainen I, Angervaniva P, Darin N, Blomqvist M RSC Adv. 2024; 14(39):28797-28806.

PMID: 39257666 PMC: 11385984. DOI: 10.1039/d4ra05520a.

Nanoscale synchrotron x-ray analysis of intranuclear iron in melanised neurons of Parkinson's substantia nigra.

Brooks J, Everett J, Hill E, Billimoria K, Morris C, Sadler P Commun Biol. 2024; 7(1):1024.

PMID: 39164395 PMC: 11335769. DOI: 10.1038/s42003-024-06636-1.

Label-Free In Situ Chemical Characterization of Amyloid Plaques in Human Brain Tissues.

Everett J, Brooks J, Tjhin V, Lermyte F, Hands-Portman I, Plascencia-Villa G ACS Chem Neurosci. 2024; 15(7):1469-1483.

PMID: 38501754 PMC: 10995949. DOI: 10.1021/acschemneuro.3c00756.

The Multifaceted Opportunities Provided by the Pheomelanin-Inspired 1,4-Benzothiazine Chromophore: A Still-Undervalued Issue.

Alfieri M, Panzella L Molecules. 2023; 28(17).

PMID: 37687069 PMC: 10488698. DOI: 10.3390/molecules28176237.

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