title: Voluntary Exercise Prevents Oxidative Stress in the Brain of Phenylketonuria Mice.
abstract: BACKGROUND
  High phenylalanine levels in phenylketonuria (PKU) have been associated with brain oxidative stress and amino acid imbalance. Exercise has been shown to improve brain function in hyperphenylalaninemia and neurodegenerative diseases. This study aimed to verify the effects of exercise on coordination and balance, plasma and brain amino acid levels, and brain oxidative stress markers in PKU mice.
  
  
  METHODS
  Twenty wild-type (WT) and 20 PAH(enu2) (PKU) C57BL/6 mice were placed in cages with (exercise, Exe) or without (sedentary, Sed) running wheels during 53 days. At day 43, a balance beam test was performed. Plasma and brain were collected for analyses of amino acid levels and the oxidative stress parameters superoxide dismutase (SOD) activity, sulfhydryl and reduced glutathione (GSH) contents, total radical-trapping antioxidant potential (TRAP), and total antioxidant reactivity (TAR).
  
  
  RESULTS
  SedPKU showed poor coordination (p < 0.001) and balance (p < 0.001), higher plasma and brain phenylalanine (p < 0.001), and increased brain oxidative stress (p < 0.05) in comparison to SedWT. ExePKU animals ran less than ExeWT (p = 0.018). Although no improvement was seen in motor coordination and balance, exercise in PKU restored SOD, sulfhydryl content, and TRAP levels to controls. TAR levels were increased in ExePKU in comparison to SedPKU (p = 0.012). Exercise decreased plasma and brain glucogenic amino acids in ExePKU, but did not change plasma and brain phenylalanine in both WT and PKU.
  
  
  CONCLUSIONS
  Exercise prevents oxidative stress in the brain of PKU mice without modifying phenylalanine levels. Hence, exercise positively affects the brain, demonstrating its value as an intervention to improve brain quality in PKU.
authors.affiliation: Department of Molecular Neurobiology, Groningen Institute for Evolutionary Life Sciences (GELIFES) - University of Groningen, Nijenborgh 7, 9747 AG, Groningen, The Netherlands. pku@priscilamazzola.com.|Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. pku@priscilamazzola.com.|Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil. pku@priscilamazzola.com.
authors.forename: Priscila Nicolao
authors.initials: PN
authors.lastname: Mazzola
authors.affiliation: Department of Molecular Neurobiology, Groningen Institute for Evolutionary Life Sciences (GELIFES) - University of Groningen, Nijenborgh 7, 9747 AG, Groningen, The Netherlands.
authors.forename: Vibeke
authors.initials: V
authors.lastname: Bruinenberg
authors.affiliation: Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Karen
authors.initials: K
authors.lastname: Anjema
authors.affiliation: Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Danique
authors.initials: D
authors.lastname: van Vliet
authors.affiliation: Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.
authors.forename: Carlos Severo
authors.initials: CS
authors.lastname: Dutra-Filho
authors.affiliation: Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Francjan J
authors.initials: FJ
authors.lastname: van Spronsen
authors.affiliation: Department of Molecular Neurobiology, Groningen Institute for Evolutionary Life Sciences (GELIFES) - University of Groningen, Nijenborgh 7, 9747 AG, Groningen, The Netherlands.
authors.forename: Eddy A
authors.initials: EA
authors.lastname: van der Zee