Numerous studies on post mortem tissue report on an increased amount of total iron in the SN also supported by large body of in vivo findings from Magnetic Resonance Imaging (MRI). Still, the local accumulation of iron in the SN in patients with PD remains a controversial issue. However, all these processes will differently affect different cell populations. Various factors have been suggested to account for increased iron accumulation in the SN of patients with PD such as, for example, dysfunction of the blood–brain barrier, altered cellular iron transport, an increased pro-inflammatory state and mutations in genes of iron transport, storage and binding. On the other hand, increased levels of iron are harmful and iron accumulations are typical hallmarks of brain ageing and several neurodegenerative disorders particularly PD. Iron deficiency, for example, is a well-established cause for impaired motor and cognitive development. Any mismatch in the demand and regional-temporal distribution of iron may result in neurological and/or mental dysfunction. In the brain, variations in iron levels correlate with its structural integrity, and there is no other organ but the CNS that is in such a constant need for readily available iron. It plays an important role as cofactor of numerous enzymes and is involved in ATP production, myelination and synthesis of DNA, RNA, proteins, and neurotransmitters. Iron is essential for a proper CNS function. 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. Quantitative trace element analysis is essential to characterise iron in oxidative processes in PD. Indeed, neuromelanin is characterised by a significantly higher loading of iron including most probable the occupancy of low-affinity iron binding sites. The highest cellular iron levels in neurons were located in the cytoplasm, which might increase the source of non-chelated Fe 3+, implicating a critical increase in the labile iron pool. While iron levels in astroglial cells remain unchanged, ferritin in oligodendroglial cells seems to be depleted by almost half in PD. 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. Distinct patterns of iron accumulation were observed across different cell populations. 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. Here, we quantified cellular iron concentrations and subcellular iron distributions 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). 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. 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. In contrast, high concentrations of free iron can be detrimental and contribute to neurodegeneration, through promotion of oxidative stress. Iron is essential for neurons and glial cells, playing key roles in neurotransmitter synthesis, energy production and myelination.
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