Jump to main content
Jump to site search

Issue 6, 2014
Previous Article Next Article

An iron–dopamine index predicts risk of parkinsonian neurodegeneration in the substantia nigra pars compacta

Author affiliations

Abstract

The co-localization of iron and dopamine raises the risk of a potentially toxic reaction. Disturbance of the balance in this unique chemical environment makes neurons in the substantia nigra pars compacta (SNc) particularly vulnerable to parkinsonian neurodegeneration in the aging brain. In Parkinson's disease, these neurons degenerate coincident with an elevation in brain iron levels, yet relatively little is known about specific regional iron distribution with respect to dopamine. To directly appraise the iron–dopamine redox couple, we applied immuno-assisted laser ablation-inductively coupled plasma-mass spectrometry imaging to co-localize iron with the dopamine-producing enzyme tyrosine hydroxylase at the coronal level of the substantia nigra. We found that in the healthy brain the SNc does not contain the greatest concentration of iron within the midbrain, while the dopamine-rich environment in this region reflects an increased oxidative load. The product of iron and dopamine was significantly greater in the SNc than the adjacent ventral tegmental area, which is less susceptible to neuron loss in Parkinson's disease. Accordingly, this ‘risk factor’ was elevated further following 6-hydroxydopamine (6-OHDA) lesioning. Considering mounting evidence that brain iron increases with age, this measurable iron–dopamine index provides direct experimental evidence of a relationship between these two redox-active chemicals in degenerating dopaminergic neurons.

Graphical abstract: An iron–dopamine index predicts risk of parkinsonian neurodegeneration in the substantia nigra pars compacta

Back to tab navigation

Supplementary files

Article information


Submitted
17 Dec 2013
Accepted
24 Jan 2014
First published
24 Jan 2014

This article is Open Access
All publication charges for this article have been paid for by the Royal Society of Chemistry

Chem. Sci., 2014,5, 2160-2169
Article type
Edge Article
Author version available

An iron–dopamine index predicts risk of parkinsonian neurodegeneration in the substantia nigra pars compacta

D. J. Hare, P. Lei, S. Ayton, B. R. Roberts, R. Grimm, J. L. George, D. P. Bishop, A. D. Beavis, S. J. Donovan, G. McColl, I. Volitakis, C. L. Masters, P. A. Adlard, R. A. Cherny, A. I. Bush, D. I. Finkelstein and P. A. Doble, Chem. Sci., 2014, 5, 2160
DOI: 10.1039/C3SC53461H

This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. Material from this article can be used in other publications provided that the correct acknowledgement is given with the reproduced material and it is not used for commercial purposes.

Reproduced material should be attributed as follows:

  • For reproduction of material from NJC:
    [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the Centre National de la Recherche Scientifique (CNRS) and the RSC.
  • For reproduction of material from PCCP:
    [Original citation] - Published by the PCCP Owner Societies.
  • For reproduction of material from PPS:
    [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the European Society for Photobiology, the European Photochemistry Association, and RSC.
  • For reproduction of material from all other RSC journals:
    [Original citation] - Published by The Royal Society of Chemistry.

Information about reproducing material from RSC articles with different licences is available on our Permission Requests page.


Social activity

Search articles by author

Spotlight

Advertisements