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

Hare, Dominic J.; Lei, Peng; Ayton, Scott; Roberts, Blaine R.; Grimm, Rudolf; George, Jessica; Bishop, David; Beavis, Alison; Donovan, Sarah J.; McColl, Gawain; Volitakis, Irene; Masters, Colin L.; Adlard, Paul A.; Cherny, Robert A.; Bush, Ashley I.; Finkelstein, David I.; Doble, Philip

doi:10.1039/c3sc53461h

Cited by 99 publications

(111 citation statements)

References 55 publications

(60 reference statements)

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“…[Cu] SNr < SNc < MRN; Figure 2e) and showed compartmentalization of Fe previously observed using LA-ICPMS, 6 The present work reports the first direct comparison of biometals quantitative imaging in single-origin neurological tissues using XFM and LA-ICPMS. We demonstrate here that both methods are useful to investigate regional biometal levels in brain tissue with high resolution.…”

Section: Analytical Chemistrymentioning

confidence: 53%

Comparative Study of Metal Quantification in Neurological Tissue Using Laser Ablation-Inductively Coupled Plasma-Mass Spectrometry Imaging and X-ray Fluorescence Microscopy

et al. 2015

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Redox-active metals in the brain mediate numerous biochemical processes and are also implicated in a number of neurodegenerative diseases. A number of different approaches are available for quantitatively measuring the spatial distribution of biometals at an image resolution approaching the subcellular level. Measured biometal levels obtained using laser ablation-inductively coupled plasma mass spectrometry (LA-ICPMS; spatial resolution 15 μm × 15 μm) were within the range of those obtained using X-ray fluorescence microscopy (XFM; spatial resolution 2 μm × 7 μm) and regional changes in metal concentration across discrete brain regions were replicated to the same degree. Both techniques are well suited to profiling changes in regional biometal distribution between healthy and diseased brain tissues, but absolute quantitation of metal levels varied significantly between methods, depending on the metal of interest. Where all possible variables affect metal levels, independent of a treatment/phenotype are controlled, either method is suitable for examining differences between experimental groups, though, as with any method for imaging post mortem brain tissue, care should be taken when interpreting the total metal levels with regard to physiological concentrations.

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Section: Analytical Chemistrymentioning

confidence: 53%

Comparative Study of Metal Quantification in Neurological Tissue Using Laser Ablation-Inductively Coupled Plasma-Mass Spectrometry Imaging and X-ray Fluorescence Microscopy

et al. 2015

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“…Several mechanisms have been proposed that induce toxicity inside the cytoplasm of neurons and also in the extracellular space, including a-synuclein/neuromelanin pathology, 148 ceruloplasmin dysfunction, 149 copper and cuproprotein dyshomeostasis 11 and an iron/dopamine-mediated oxidative stress cycle. 150 Dopaminergic neurons are particularly vulnerable to oxidative damage, potentially due to their propensity to accumulate iron with age, 151,152 and thus oxidative stress presents a central role on PD pathogenesis, [153][154][155] and a logical target of selenoprotein antioxidant activity.…”

Section: Parkinson's Diseasementioning

confidence: 99%

Selenium, selenoproteins and neurodegenerative diseases

et al. 2015

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It is unsurprising that our understanding of the role of selenium in neurological function is somewhat immature, considering its relatively recent discovery as an essential element to human health. Selenocysteine, the 21st amino acid, is the defining feature of the 25 selenoprotein-encoding genes so far discovered within the human genome. The low abundance of these proteins in the brain belies the integral role they play in normal neurological function, from well-characterised antioxidant activity in the periphery to poorly understood mechanisms that modulate mitochondrial function and response to brain pathology. Selenium has been identified as playing a role in several neurodegenerative disorders, including Alzheimer's and Parkinson's disease, though its function as a 'cause or effect' of disease process remains unclear. This review discusses selenium metabolism in detail, specifically with regard to the role it plays within the central nervous system, and examines the most current literature investigating how selenium may be involved in chronic diseases of the central nervous system.

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“…Introduction of extra labile iron-as might occur through exposure to high levels of iron in infant formula during early lifeinto the cytoplasm of cells that produce high concentrations of a potent biological reductant, such as dopamine, might result in increased oxidative stress. 99 Measuring iron exposure Numerous obstacles hinder our understanding of the relationship between iron exposure after birth and neuronal degeneration in senescence. The biological half-life of circulating iron in adults is approximately 3 years for women (increasing to 4 years after the menopause) and 8 years for men, 100 so blood levels are not a suitable measure of exposure to iron in the distant past.…”

Section: Contribution Of Early-life Exposurementioning

confidence: 99%

Is early-life iron exposure critical in neurodegeneration?

et al. 2015

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The effects of iron deficiency are well documented, but relatively little is known about the long-term implications of iron overload during development. High levels of redox-active iron in the brain have been associated with neurodegenerative disorders, most notably Parkinson disease, yet a gradual increase in brain iron seems to be a feature of normal ageing. Increased brain iron levels might result from intake of infant formula that is excessively fortified with iron, thereby altering the trajectory of brain iron uptake and amplifying the risk of iron-associated neurodegeneration in later life. In this Perspectives article, we discuss the potential long-term implications of excessive iron intake in early life, propose the analysis of iron deposits in teeth as a method for retrospective determination of iron exposure during critical developmental windows, and call for evidence-based optimization of the chemical composition of infant dietary supplements.

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

Abstract: Imaging of iron and dopamine by laser ablation-inductively coupled plasma-mass spectrometry reveals a risk index for parkinsonian neurodegeneration

Cited by 99 publications

References 55 publications

Comparative Study of Metal Quantification in Neurological Tissue Using Laser Ablation-Inductively Coupled Plasma-Mass Spectrometry Imaging and X-ray Fluorescence Microscopy

Comparative Study of Metal Quantification in Neurological Tissue Using Laser Ablation-Inductively Coupled Plasma-Mass Spectrometry Imaging and X-ray Fluorescence Microscopy

Selenium, selenoproteins and neurodegenerative diseases

Is early-life iron exposure critical in neurodegeneration?

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