title: Effects of Neonatal Iron Feeding and Chronic Clioquinol Administration on the Parkinsonian Human A53T Transgenic Mouse.
abstract: Increased nigral iron (Fe) is a cardinal feature of Parkinson's disease, as is the accumulation of aggregates comprising α-synuclein. We used wild-type mice and transgenic mice overexpressing the human A53T mutation to α-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 α-synuclein, presents a disease phenotype resistant to intervention using clioquinol later in life.
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne , Parkville, Victoria 3052, Australia.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Billings
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne , Parkville, Victoria 3052, Australia.|Elemental Bio-imaging Facility, University of Technology Sydney , Broadway, New South Wales 2007, Australia.
authors.forename: Dominic J
authors.initials: DJ
authors.lastname: Hare
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne , Parkville, Victoria 3052, Australia.
authors.forename: Milawaty
authors.initials: M
authors.lastname: Nurjono
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne , Parkville, Victoria 3052, Australia.
authors.forename: Irene
authors.initials: I
authors.lastname: Volitakis
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne , Parkville, Victoria 3052, Australia.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Cherny
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne , Parkville, Victoria 3052, Australia.
authors.forename: Ashley I
authors.initials: AI
authors.lastname: Bush
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne , Parkville, Victoria 3052, Australia.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Adlard
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne , Parkville, Victoria 3052, Australia.
authors.forename: David I
authors.initials: DI
authors.lastname: Finkelstein
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D007464:Clioquinol / Q000494:pharmacology*; D004195:Disease Models, Animal; D006801:Humans; D007501:Iron / Q000633:toxicity*; D007502:Iron Chelating Agents / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009043:Motor Activity / Q000187:drug effects; D020734:Parkinsonian Disorders; D010641:Phenotype
chemical_list: D007502:Iron Chelating Agents; D007464:Clioquinol; D007501:Iron
keywords: Parkinson’s disease; alpha-synuclein; dietary iron; iron accumulation; risk factor