Journal
ACS CHEMICAL NEUROSCIENCE
Volume 7, Issue 3, Pages 360-366Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acschemneuro.5b00305
Keywords
Parkinson's disease; alpha-synuclein; iron accumulation; dietary iron; risk factor
Funding
- National Health and Medical Research Council
- Australian Research Council
- Victorian Government
- Operational Infrastructure Support Grant
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Increased nigral iron (Fe) is a cardinal feature of Parkinson's disease, as is the accumulation of aggregates comprising a-synuclein. We used wild-type mice and transgenic mice over-expressing the human A53T mutation to alpha-synuclein to examine the influence of increased Fe (days 10-17 postpartum) on the parkinsonian development phenotype of these animals (including abnormal nigral Fe levels and deficits in both cell numbers and locomotor activity), and to explore the impact of the Fe chelator clioquinol in the model. Both untreated and Fe-loaded A53T mice showed similar levels of nigral cell loss, though 5 months of clioquinol treatment was only able to prevent the loss in the non-Fe-loaded A53T group. Iron levels in the Fe-loaded A53T mice returned to normal at 8 months, though effects of dopamine denervation remained, demonstrated by limited locomotor activity and sustained neuron loss. These data suggest that Fe exposure during a critical developmental window, combined with the overexpression mutant a-synuclein, presents a disease phenotype resistant to intervention using clioquinol later in life.
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