Cited by 156Parkinson's Disease Mechanisms and TreatmentsNeurological diseases and metabolismIron Metabolism and Disorders

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Degeneration of nigrostriatal dopaminergic neurons increases iron within the substantia nigra: a histochemical and neurochemical study

Oestreicher, E., Sengstock, G.J., Riederer, P., Olanow, C.W., Dunn, A.J., Arendash, G.W.·1994·Brain Research

DOI 10.1016/0006-8993(94)90833-8

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Abstract

Parkinson's-diseased (PD) brains have increased levels of iron in the zona compacta of the substantia nigra (SNc). To determine whether these elevated nigral iron levels may be caused secondarily by degeneration of nigrostriatal dopaminergic (NS-DA) neurons, the NS-DA pathway was unilaterally lesioned in rats through 6-hydroxydopamine (6-OHDA) infusion and nigral iron levels evaluated three weeks later. A significant increase was observed in both iron concentration (+35%) and iron content (+33) within the substantia nigra (SN) ipsilateral to comprehensive 6-OHDA lesions. Moreover, ferric iron staining was dramatically increased within the SNc following 6-OHDA lesions, primarily due to the appearance of iron-positive SNc neurons and infiltrating reactive glial cells. Iron staining in the SN zona reticularis was modestly increased after 6-OHDA lesions, but staining in the neostriatum and globus pallidus was unaffected. These results indicate that loss of NS-DA neurons is associated with increased iron levels in the SN. This suggests that increased nigral iron levels in PD may be secondary to some neurodegenerative process. Nonetheless, even a secondary increase in nigral iron levels may be of pathogenic importance in PD because of iron's ability to catalyze neurotoxic free radical formation and perpetuate neurodegeneration.

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Authors: Oestreicher, E., Sengstock, G. J., Riederer, P., Olanow, C. W., Dunn, A. J., & Arendash, G. W.
Affiliations: University of Würzburg (DE)
University of South Florida (US)
Louisiana State University (US)
Corresponding author: Arendash, G.W.
ORCID: Riederer, P.
Olanow, C.W.
Arendash, G.W.
Venue: Brain Research
Publisher: Elsevier BV
Published: 1994-10
Volume: 660
Issue: 1
Pages: 8-18
ISSN: 0006-8993 (ISSN-L)
DOI: 10.1016/0006-8993(94)90833-8
OpenAlex: W2049800884
Cited by: 156
References: 47
Citations by year: 2026: 1 · 2025: 1 · 2023: 4 · 2022: 7 · 2021: 7 · 2020: 3 · 2019: 2 · 2018: 2 · 2017: 3 · 2016: 1 · 2015: 4 · 2014: 5 · 2013: 7 · 2012: 4
FWCI: 3.39
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Brain Research (publishedVersion)
PubMed (publishedVersion)
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, nigrostriatal dopaminergic neurons, substantia nigra, iron accumulation, 6-hydroxydopamine lesion, neurodegeneration, reactive glial cells
MeSH terms: Amphetamine, Animals, Behavior, Animal, Corpus Striatum, Histocytochemistry, Iron, Male, Medial Forebrain Bundle, Nerve Degeneration, Neurons, Stereotyped Behavior, Substantia Nigra, Oxidopamine, Rats, Sprague-Dawley, Rats

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Degeneration of nigrostriatal dopaminergic neurons increases iron within the substantia nigra: a histochemical and neurochemical study

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