title: Iron accumulation and dysregulation in the putamen in fragile X-associated tremor/ataxia syndrome.
abstract: Fragile X-associated tremor/ataxia syndrome is an adult-onset disorder associated with premutation alleles of the FMR1 gene. This disorder is characterized by progressive action tremor, gait ataxia, and cognitive decline. Fragile X-associated tremor/ataxia syndrome pathology includes dystrophic white matter and intranuclear inclusions in neurons and astrocytes. We previously demonstrated that the transport of iron into the brain is altered in fragile X-associated tremor/ataxia syndrome; therefore, we also expect an alteration of iron metabolism in brain areas related to motor control. Iron is essential for cell metabolism, but uncomplexed iron leads to oxidative stress and contributes to the development of neurodegenerative diseases. We investigated a potential iron modification in the putamen - a structure that participates in motor learning and performance - in fragile X-associated tremor/ataxia syndrome.
  
  
  
  We used samples of putamen obtained from 9 fragile X-associated tremor/ataxia syndrome and 9 control cases to study iron localization using Perl's method, and iron-binding proteins using immunostaining.
  
  
  
  We found increased iron deposition in neuronal and glial cells in the putamen in fragile X-associated tremor/ataxia syndrome. We also found a generalized decrease in the amount of the iron-binding proteins transferrin and ceruloplasmin, and decreased number of neurons and glial cells that contained ceruloplasmin. However, we found increased levels of iron, transferrin, and ceruloplasmin in microglial cells, indicating an attempt by the immune system to remove the excess iron.
  
  
  
  Overall, found a deficit in proteins that eliminate extra iron from the cells with a concomitant increase in the deposit of cellular iron in the putamen in Fragile X-associated tremor/ataxia syndrome. © 2017 International Parkinson and Movement Disorder Society.
authors.affiliation: Department of Pathology and Laboratory Medicine, UC Davis School of Medicine, and the Institute for Pediatric Regenerative Medicine and Shriners Hospitals for Children of Northern California, Sacramento, California.
authors.forename: Jeanelle
authors.initials: J
authors.lastname: Ariza
authors.affiliation: Department of Pathology and Laboratory Medicine, UC Davis School of Medicine, and the Institute for Pediatric Regenerative Medicine and Shriners Hospitals for Children of Northern California, Sacramento, California.
authors.forename: Hailee
authors.initials: H
authors.lastname: Rogers
authors.affiliation: Department of Pathology and Laboratory Medicine, UC Davis School of Medicine, and the Institute for Pediatric Regenerative Medicine and Shriners Hospitals for Children of Northern California, Sacramento, California.
authors.forename: Anna
authors.initials: A
authors.lastname: Hartvigsen
authors.affiliation: Department of Pathology and Laboratory Medicine, UC Davis School of Medicine, and the Institute for Pediatric Regenerative Medicine and Shriners Hospitals for Children of Northern California, Sacramento, California.
authors.forename: Melissa
authors.initials: M
authors.lastname: Snell
authors.affiliation: Department of Pathology and Laboratory Medicine, UC Davis School of Medicine, and the Institute for Pediatric Regenerative Medicine and Shriners Hospitals for Children of Northern California, Sacramento, California.
authors.forename: Michael
authors.initials: M
authors.lastname: Dill
authors.affiliation: Department of Pathology and Laboratory Medicine, UC Davis School of Medicine, and the Institute for Pediatric Regenerative Medicine and Shriners Hospitals for Children of Northern California, Sacramento, California.
authors.forename: Derek
authors.initials: D
authors.lastname: Judd
authors.affiliation: MIND Institute, UC Davis Medical Center, Sacramento, California.|Department of Biochemistry and Molecular Medicine, UC Davis School of Medicine, Sacramento, California.
authors.forename: Paul
authors.initials: P
authors.lastname: Hagerman
authors.affiliation: Department of Pathology and Laboratory Medicine, UC Davis School of Medicine, and the Institute for Pediatric Regenerative Medicine and Shriners Hospitals for Children of Northern California, Sacramento, California.|MIND Institute, UC Davis Medical Center, Sacramento, California.
authors.forename: Verónica
authors.initials: V
authors.lastname: Martínez-Cerdeño
mesh_terms: D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D001259:Ataxia / Q000235:genetics / Q000473:pathology*; D016022:Case-Control Studies; D002531:Cerebellum / Q000473:pathology; D002570:Ceruloplasmin / Q000378:metabolism; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics; D005600:Fragile X Syndrome / Q000235:genetics / Q000473:pathology*; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008297:Male; D011699:Putamen / Q000378:metabolism*; D014168:Transferrin / Q000378:metabolism; D014202:Tremor / Q000235:genetics / Q000473:pathology*
chemical_list: D002570:Ceruloplasmin; D051860:Fragile X Messenger Ribonucleoprotein 1; D007501:Iron; D014168:Transferrin; C497683:FMR1 protein, human
keywords: CGG; FXTAS; dementia; fragile X; motor disorder; neurodegeneration; repeat-expansion disorder