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

E. Oestreicher, G. J. Sengstock, P. Riederer, C. W. Olanow, A. J. Dunn, G. W. Arendash

Research output: Contribution to journalArticle

129 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)8-18
Number of pages11
JournalBrain Research
Volume660
Issue number1
DOIs
StatePublished - Oct 10 1994

Keywords

  • Dopamine
  • Iron
  • Nigrostriatal degeneration
  • Substantia nigra

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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