Direct chemical imaging of neuromelanin in the most vulnerable brain cells in Parkinson’s disease

Authors: Jake Brooks (University of Warwick) , Joanna Collingwood (Warwick University)
Co-authored by industrial partner: No

Type: Diamond Annual Review Highlight

State: Published (Approved)
Published: July 2021
Diamond Proposal Number(s): 15230 , 15854 , 20809 , 24526 , 24531

Abstract: Parkinson’s disease causes the loss of a particular group of brain cells, the neurons that produce the neurotransmitter dopamine. As these cells contain a dark pigment, neuromelanin, the change is evident from the loss of pigment in this brain region. Characterisation of neuromelanin in tissue remains dependent on visible pigmentation. Faint pigmentation may be interpreted as cell loss, and so contrast- enhancing stains are commonly used. However, this staining constrains further chemical analysis of the tissue. Researchers explored the use of synchrotron X-ray microscopy to visualise neuromelanin without relying on visible pigmentation or chemical staining. They performed combined imaging and spectroscopy (spectromicroscopy) on Diamond Light Source’s Scanning X-ray Microscopy beamline (I08), allowing the creation of images from distinct X-ray absorption features. Nanoscale spatial resolution using soft (low energy) X-rays allowed the researchers to probe the organic structure of neuromelanin to seek distinguishing spectral features. This revealed a characteristic feature in the absorption spectrum for neuromelanin. The team used this feature to create maps of neuromelanin distributions, which matched those observed in stained tissue sections. The team also used nanoscale X-ray Fluorescence (XRF) with hard (high energy) X-rays on the Hard X-ray Nanoprobe beamline (I14) to discover a signature for identifying neuromelanin. This showed that neuromelanin could be identified by its elevated sulfur content. However, this approach is not as specific to neuromelanin as the soft X-ray method. The discovery of the soft X-ray neuromelanin signature offers significant potential for non-destructive studies of the relationships between depigmentation, metal binding and neurodegeneration in Parkinson’s disease.

Journal Keywords: Neuromelanin; Parkinson’s Disease; Spectromicroscopy

Diamond Keywords: Parkinson’s Disease

Subject Areas: Biology and Bio-materials, Chemistry, Technique Development


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

Added On: 12/11/2021 13:42

Discipline Tags:

Neurodegenerative Diseases Non-Communicable Diseases Health & Wellbeing Biochemistry Technique Development - Life Sciences & Biotech Neurology Chemistry Organic Chemistry Life Sciences & Biotech

Technical Tags:

Imaging Microscopy X-ray Fluorescence (XRF) X-ray Microscopy Scanning X-ray Microscopy