Cited by 273Parkinson's Disease Mechanisms and TreatmentsNeurological diseases and metabolismIron Metabolism and Disorders

Individual dopaminergic neurons show raised iron levels in Parkinson disease

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Oakley, A. E., Collingwood, J. F., Dobson, J., Love, G., Perrott, H. R., Edwardson, J. A., Elstner, M., Morris, C. M.·2007·Neurology

Abstract

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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Crossref · 10.1212/01.wnl.0000262033.01945.9a

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  • HIF-2α knockout mice 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.

    “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).”
  • HIF-2α, but not HIF-1α, specifically activated an HRE located ∼2 kb upstream from the transcription-initiation site of the mouse frataxin gene.

    “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).”

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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
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 › 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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