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Individual dopaminergic neurons show raised iron levels in Parkinson disease
Open accessAbstract
OBJECTIVE: Evidence suggests that abnormal iron metabolism is associated with Parkinson disease (PD), with raised iron levels found in pathologically affected areas in PD. It is unknown if this elevated iron is actually associated with neurons or reactive glia, and we therefore addressed this issue by determining if raised iron was present in single dopaminergic neurons. METHODS: We used unfixed frozen sections from postmortem tissue of PD patients and elderly normal individuals to avoid metal contamination and translocation. Levels of iron and other elements were measured using sensitive and specific wavelength dispersive electron probe x-ray microanalysis coupled with cathodoluminescence spectroscopy in individual substantia nigra dopaminergic neurons. RESULTS: We identified raised intraneuronal iron in single defined substantia nigra neurons in PD (mean neuronal iron 2,838 vs 1,611, p < 0.0001) but not in other movement disorders such as Huntington disease. These findings were unrelated to the density of remaining neurons. CONCLUSIONS: Primary changes in neuronal iron could lead to neurodegeneration in Parkinson disease.
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“Recently, HIF-2α knockout mice were shown to have impaired mitochondrial respiration, sensitized mitochondrial permeability transition pore opening, and reduced activity of aconitase, because of marked reduction of frataxin mRNA expression in HIF-2α−/−livers (224).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [224]
In the citing paper
“Indeed, HIF-2α, but not HIF-1α, specifically activated an HRE that is located ∼2 kb upstream from the transcription-initiation site of the mouse frataxin gene (224).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [224]
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Metadata
- Authors
- Oakley, A. E., Collingwood, J. F., Dobson, J., Love, G., Perrott, H. R., Edwardson, J. A., Elstner, M., & Morris, C. M.
- Affiliations
- University of Bath (GB)
- Venue
- Neurology
- Published
- 2007-05-22
- Volume
- 68
- Issue
- 21
- Pages
- 1820-1825
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- OpenAlex
- W2100919899
- Cited by
- 273
- References
- 37
- Citations by year
- 2026: 8 · 2025: 10 · 2024: 12 · 2023: 9 · 2022: 18 · 2021: 16 · 2020: 20 · 2019: 14 · 2018: 11 · 2017: 19 · 2016: 15 · 2015: 11 · 2014: 17 · 2013: 15 · 2012: 12
- FWCI
- 11.23
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Locations
- Neurology (publishedVersion)
- PubMed (publishedVersion)
- Newcastle University ePrints (Newcastle Univesity)
- Funders
- Engineering and Physical Sciences Research Council (EP/D066654/1)
- National Institute on Aging (R01 AG 02030-01)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Keywords
- Parkinson's disease, dopaminergic neurons, substantia nigra, iron metabolism, neurodegeneration, Huntington's disease, reactive glia
- MeSH terms
- Adult, Aged, Aged, 80 and over, Brain Chemistry, Cell Count, Dopamine, Electron Probe Microanalysis, Ferritins, Humans, Iron, Middle Aged, Neuroglia, Neurons, Parkinson Disease, Predictive Value of Tests, Spectrum Analysis, Substantia Nigra, Biomarkers, Up-Regulation, Iron Metabolism Disorders, Neuropil
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