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  Cell specific quantitative iron mapping on brain slices by immuno-μPIXE in healthy elderly and Parkinson’s disease

Friedrich, I., Reimann, K., Jankuhn, S., Kirilina, E., Stieler, J., Sonntag, M., et al. (2021). Cell specific quantitative iron mapping on brain slices by immuno-μPIXE in healthy elderly and Parkinson’s disease. Acta Neuropathologica, 9(1): 47. doi:10.1186/s40478-021-01145-2.

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 Creators:
Friedrich , I.1, Author
Reimann, Katja1, Author
Jankuhn, S.2, Author
Kirilina, Evgeniya3, 4, Author              
Stieler, J.1, Author
Sonntag, M.1, Author
Meijer, Jan2, Author
Weiskopf, Nikolaus2, 3, Author              
Reinert, Tilo2, 3, Author              
Arendt, Thomas1, Author
Morawski, M.1, 3, Author
Affiliations:
1Paul Flechsig Institute for Brain Research, University of Leipzig, Germany, ou_persistent22              
2Felix Bloch Institute for Solid State Physics, University of Leipzig, Germany, ou_persistent22              
3Department Neurophysics (Weiskopf), MPI for Human Cognitive and Brain Sciences, Max Planck Society, Leipzig, DE, ou_2205649              
4Center for Cognitive Neuroscience Berlin (CCNB), FU Berlin, Germany, ou_persistent22              

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 Abstract: Iron is essential for neurons and glial cells, playing key roles in neurotransmitter synthesis, energy production and myelination. In contrast, high concentrations of free iron can be detrimental and contribute to neurodegeneration, through promotion of oxidative stress. Particularly in Parkinson’s disease (PD) changes in iron concentrations in the substantia nigra (SN) was suggested to play a key role in degeneration of dopaminergic neurons in nigrosome 1. However, the cellular iron pathways and the mechanisms of the pathogenic role of iron in PD are not well understood, mainly due to the lack of quantitative analytical techniques for iron quantification with subcellular resolution. Here, we quantified cellular iron concentrations and subcellular iron distribution in dopaminergic neurons and different types of glial cells in the SN both in brains of PD patients and in non-neurodegenerative control brains (Co). To this end, we combined spatially resolved quantitative element mapping using micro particle induced X-ray emission (μPIXE) with nickel-enhanced immunocytochemical detection of cell type-specific antigens allowing to allocate element-related signals to specific cell types. Distinct patterns of iron accumulation were observed across different cell populations. In the control (Co) SNc, oligodendroglial and astroglial cells hold the highest cellular iron concentration whereas in PD, the iron concentration was increased in most cell types in the substantia nigra except for astroglial cells and ferritin-positive oligodendroglial cells. While iron levels in astroglial cells remain unchanged, ferritin in oligodendroglial cells seems to be depleted by almost half in PD. The highest cellular iron levels in neurons were located in the cytoplasm, which might increase the source of non-chelated Fe3+, implicating a critical increase in the labile iron pool. Indeed, neuromelanin is characterised by a significantly higher loading of iron including most probable the occupancy of low-affinity iron binding sites. Quantitative trace element analysis is essential to characterise iron in oxidative processes in PD. The quantification of iron provides deeper insights into changes of cellular iron levels in PD and may contribute to the research in iron-chelating disease-modifying drugs.

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Language(s): eng - English
 Dates: 2020-12-132021-02-282021-03-22
 Publication Status: Published online
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 Rev. Type: -
 Identifiers: DOI: 10.1186/s40478-021-01145-2
PMID: 33752749
PMC: PMC7986300
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Grant ID : MO 2249/3-1 and MO 2249/3-2
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Funding organization : Deutsche Forschungsgemeinschaft (DFG)
Project name : -
Grant ID : AFI#18072
Funding program : -
Funding organization : Alzheimer Forschung Initiative
Project name : -
Grant ID : FP7/2007-2013
Funding program : -
Funding organization : European Union
Project name : -
Grant ID : 616905
Funding program : -
Funding organization : European Research Counsil
Project name : Horizon 2020
Grant ID : 681094
Funding program : -
Funding organization : European Union
Project name : -
Grant ID : 01EW1711A & B
Funding program : -
Funding organization : Bundesministerium für Bildung und Forschung

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Title: Acta Neuropathologica
  Other : Acta Neuropathol.
Source Genre: Journal
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Pages: - Volume / Issue: 9 (1) Sequence Number: 47 Start / End Page: - Identifier: ISSN: 0001-6322
CoNE: https://pure.mpg.de/cone/journals/resource/954925374814_1