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.
Highlights
Visualization of neuromelanin (NM), a biological polymer formed by autoxidation of dopamine and cysteine within dopamine and noradrenaline synthesizing neurons, historically relied on the presence of visible pigmentation, with or [+] These authors contributed to this work
Neuromelanin contrast arising from the spectral feature centered at 287.4 eV was consistently observed in substantia nigra tissue from the five independent cases, irrespective of disease classification (Table S1)
We have shown that a characteristic peak in the carbon Kedge x-ray absorption spectrum of neuromelanin can be used as a basis for label-free mapping of neuromelanin in human brain tissue
Summary
Visualization of neuromelanin (NM), a biological polymer formed by autoxidation of dopamine and cysteine within dopamine and noradrenaline synthesizing neurons, historically relied on the presence of visible pigmentation, with or [+] These authors contributed to this work. In 1988, Hirsch and co-workers highlighted how this, by definition, restricts NM visualization to forms of NM with detectable pigment, thereby excluding clusters that are too faint to view using light microscopy.[1] This need for a neuromelanin-specific marker has not been met in over three decades, with studies continuing to depend on the natural contrast of the NM pigment viewed under an optical or electron microscope.[2] This constrains objective investigation of NM in human health and disease, and in other species in which pigmentation is less apparent, carrying an implicit suggestion that the quantity of NM is proportional to the detectable pigmentation
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