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

Hare, DJ; Lei, P; Ayton, S; Roberts, BR; Grimm, R; George, JL; Bishop, DP; Beavis, AD; Donovan, SJ; McColl, G; Volitakis, I; Masters, CL; Adlard, PA; Cherny, RA; Bush, AI; Finkelstein, DI; Doble, PA

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

Hare, DJ

Lei, P Ayton, S Roberts, BR Grimm, R George, JL Bishop, DP

Beavis, AD

Donovan, SJ McColl, G Volitakis, I Masters, CL Adlard, PA Cherny, RA Bush, AI Finkelstein, DI Doble, PA

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Publication Type:: Journal Article
Citation:: Chemical Science, 2014, 5 (6), pp. 2160 - 2169
Issue Date:: 2014-01-01

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Field	Value	Language
dc.contributor.author	Hare, DJ https://orcid.org/0000-0002-5922-7643	en_US
dc.contributor.author	Lei, P	en_US
dc.contributor.author	Ayton, S	en_US
dc.contributor.author	Roberts, BR	en_US
dc.contributor.author	Grimm, R	en_US
dc.contributor.author	George, JL	en_US
dc.contributor.author	Bishop, DP https://orcid.org/0000-0002-6533-4410	en_US
dc.contributor.author	Beavis, AD https://orcid.org/0000-0001-6259-7699	en_US
dc.contributor.author	Donovan, SJ	en_US
dc.contributor.author	McColl, G	en_US
dc.contributor.author	Volitakis, I	en_US
dc.contributor.author	Masters, CL	en_US
dc.contributor.author	Adlard, PA	en_US
dc.contributor.author	Cherny, RA	en_US
dc.contributor.author	Bush, AI	en_US
dc.contributor.author	Finkelstein, DI	en_US
dc.contributor.author	Doble, PA https://orcid.org/0000-0002-8472-1301	en_US
dc.date.issued	2014-01-01	en_US
dc.identifier.citation	Chemical Science, 2014, 5 (6), pp. 2160 - 2169	en_US
dc.identifier.issn	2041-6520	en_US
dc.identifier.uri	http://hdl.handle.net/10453/32801
dc.identifier.uri	http://hdl.handle.net/10453/29630
dc.description.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. This journal is © the Partner Organisations 2014.	en_US
dc.relation.ispartof	Chemical Science	en_US
dc.relation.isbasedon	10.1039/c3sc53461h	en_US
dc.title	An iron-dopamine index predicts risk of parkinsonian neurodegeneration in the substantia nigra pars compacta	en_US
dc.type	Journal Article
utslib.citation.volume	6	en_US
utslib.citation.volume	5	en_US
utslib.for	0301 Analytical Chemistry	en_US
utslib.for	03 Chemical Sciences	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Mathematical and Physical Sciences
pubs.organisational-group	/University of Technology Sydney/Strength - CFS - Centre for Forensic Science
utslib.copyright.status	closed_access
pubs.issue	6	en_US
pubs.publication-status	Published	en_US
pubs.volume	5	en_US

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. This journal is © the Partner Organisations 2014.

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http://hdl.handle.net/10453/29630