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

Brooks, Jake; Everett, James; Lermyte, Frederik; Tjhin, Vindy Tjendana; Banerjee, Samya; O’Connor, Peter B.; Morris, Christopher M.; Sadler, Peter J.; Telling, Neil D.; Collingwood, Joanna F.

doi:10.1002/ange.202000239

Cited by 2 publications

(2 citation statements)

References 39 publications

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“…Following dehydration, amyloid plaque cores were embedded in an STXM-compatible resin composed of an equimolar mixture of trimethylolpropane triglycidyl ether: 4,4′-methylenebis (2-methylcyclohexylamine). This resin has previously been used successfully by our group to examine biological tissues using x-ray spectromicroscopy ( 15 , 39 , 68 – 70 ). Resin polymerization occurred at 60°C over a period of 24 hours.…”

Section: Methodsmentioning

confidence: 99%

“…These standards were prepared to assess the effect of the embedding process and to confirm that the STXM measurements did not alter the oxidation state of metals embedded within an organic matrix. An additional ferric (Fe 3+ ) iron standard was also prepared in an organic polymer matrix [as described by Brooks et al ( 68 )] to further assess the effect on iron oxidation state of successive x-ray beam doses. To avoid cross-contamination of samples, the preparation of metal nanoparticle standards was performed after the preparation and storage of amyloid plaque core materials.…”

Section: Methodsmentioning

confidence: 99%

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Biogenic metallic elements in the human brain?

et al. 2021

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The chemistry of copper and iron plays a critical role in normal brain function. A variety of enzymes and proteins containing positively charged Cu+, Cu2+, Fe2+, and Fe3+ control key processes, catalyzing oxidative metabolism and neurotransmitter and neuropeptide production. Here, we report the discovery of elemental (zero–oxidation state) metallic Cu0 accompanying ferromagnetic elemental Fe0 in the human brain. These nanoscale biometal deposits were identified within amyloid plaque cores isolated from Alzheimer’s disease subjects, using synchrotron x-ray spectromicroscopy. The surfaces of nanodeposits of metallic copper and iron are highly reactive, with distinctly different chemical and magnetic properties from their predominant oxide counterparts. The discovery of metals in their elemental form in the brain raises new questions regarding their generation and their role in neurochemistry, neurobiology, and the etiology of neurodegenerative disease.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Biogenic metallic elements in the human brain?

et al. 2021

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

Brooks,

Everett,

Hill

et al. 2024

Commun Biol

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Neuromelanin-pigmented neurons of the substantia nigra are selectively lost during the progression of Parkinson’s disease. These neurons accumulate iron in the disease state, and iron-mediated neuron damage is implicated in cell death. Animal models of Parkinson’s have evidenced iron loading inside the nucleoli of nigral neurons, however the nature of intranuclear iron deposition in the melanised neurons of the human substantia nigra is not understood. Here, scanning transmission x-ray microscopy (STXM) is used to probe iron foci in relation to the surrounding ultrastructure in melanised neurons of human substantia nigra from a confirmed Parkinson’s case. In addition to the expected neuromelanin-bound iron, iron deposits are also associated with the edge of the cell nucleolus. Speciation analysis confirms these deposits to be ferric (Fe3+) iron. The function of intranuclear iron in these cells remains unresolved, although both damaging and protective mechanisms are considered. This finding shows that STXM is a powerful label-free tool for the in situ, nanoscale chemical characterisation of both organic and inorganic intracellular components. Future applications are likely to shed new light on incompletely understood biochemical mechanisms, such as metal dysregulation and morphological changes to cell nucleoli, that are important in understanding the pathogenesis of Parkinson’s.

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

Cited by 2 publications

References 39 publications

Biogenic metallic elements in the human brain?

Biogenic metallic elements in the human brain?

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

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