title: Neonatal Iron Supplementation Induces Striatal Atrophy in Female YAC128 Huntington's Disease Mice.
abstract: BACKGROUND
  Dysregulation of iron homeostasis is implicated in the pathogenesis of Huntington's disease. We have previously shown that increased iron intake in R6/2 HD neonatal mice, but not adult R6/2 HD mice potentiates disease outcomes at 12-weeks of age corresponding to advanced HD [Redox Biol. 2015;4 : 363-74]. However, whether these findings extend to other HD models is unknown. In particular, it is unclear if increased neonatal iron intake can promote neurodegeneration in mouse HD models where disease onset is delayed to mid-adult life.
  
  
  OBJECTIVE
  To determine if increased dietary iron intake in neonatal and adult life-stages potentiates HD in the slowly progressive YAC128 HD mouse model.
  
  
  METHODS
  Female neonatal mice were supplemented daily from days 10-17 with 120μg/g body weight of carbonyl iron. Adult mice were provided diets containing low (50 ppm), medium (150 ppm) and high (500 ppm) iron concentrations from 2-months of age. HD progression was determined using behavioral, brain morphometric and biochemical approaches.
  
  
  RESULTS
  Neonatal-iron supplemented YAC128 HD mice had significantly lower striatal volumes and striatal neuronal cell body volumes as compared to control HD mice at 1-year of age. Neonatal-iron supplementation of HD mice had no effect on rota-rod motor endurance and brain iron or glutathione status. Adult iron intake level had no effect on HD progression. YAC128 HD mice had altered peripheral responses to iron intake compared to iron-matched wild-type controls.
  
  
  CONCLUSIONS
  Female YAC128 HD mice supplemented with nutritionally-relevant levels of iron as neonates demonstrate increased striatal degeneration 1-year later.
authors.affiliation: Department of Veterinary Sciences, University of Wyoming, Laramie, WY, USA.
authors.forename: Kiersten L
authors.initials: KL
authors.lastname: Berggren
authors.affiliation: Department of Veterinary Sciences, University of Wyoming, Laramie, WY, USA.|Neuroscience Graduate Program, University of Wyoming, Laramie, WY, USA.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Department of Veterinary Sciences, University of Wyoming, Laramie, WY, USA.
authors.forename: Julia A
authors.initials: JA
authors.lastname: Fox
authors.affiliation: Department of Zoology and Physiology, University of Wyoming, Laramie, WY, USA.
authors.forename: Megan
authors.initials: M
authors.lastname: Dudenhoeffer
authors.affiliation: Department of Veterinary Sciences, University of Wyoming, Laramie, WY, USA.
authors.forename: Sonal
authors.initials: S
authors.lastname: Agrawal
authors.affiliation: Department of Veterinary Sciences, University of Wyoming, Laramie, WY, USA.|Neuroscience Graduate Program, University of Wyoming, Laramie, WY, USA.
authors.forename: Jonathan H
authors.initials: JH
authors.lastname: Fox
mesh_terms: D000818:Animals; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D006651:Histocytochemistry; D006816:Huntington Disease / Q000378:metabolism*; D019266:Iron, Dietary / Q000008:administration & dosage / Q000009:adverse effects* / Q000378:metabolism*; D051379:Mice
chemical_list: D019266:Iron, Dietary
keywords: Huntington’s disease; dietary iron; mouse model; neurodegeneration