title: An Abnormal Nitric Oxide Metabolism Contributes to Brain Oxidative Stress in the Mouse Model for the Fragile X Syndrome, a Possible Role in Intellectual Disability.
abstract: BACKGROUND
  Fragile X syndrome is the most common genetic cause of mental disability. Although many research has been performed, the mechanism underlying the pathogenesis is unclear and needs further investigation. Oxidative stress played major roles in the syndrome. The aim was to investigate the nitric oxide metabolism, protein nitration level, the expression of NOS isoforms, and furthermore the activation of the nuclear factor NF-κB-p65 subunit in different brain areas on the fragile X mouse model.
  
  
  METHODS
  This study involved adult male Fmr1-knockout and wild-type mice as controls. We detected nitric oxide metabolism and the activation of the nuclear factor NF-κBp65 subunit, comparing the mRNA expression and protein content of the three NOS isoforms in different brain areas.
  
  
  RESULTS
  Fmr1-KO mice showed an abnormal nitric oxide metabolism and increased levels of protein tyrosine nitrosylation. Besides that, nuclear factor NF-κB-p65 and inducible nitric oxide synthase appeared significantly increased in the Fmr1-knockout mice. mRNA and protein levels of the neuronal nitric oxide synthase appeared significantly decreased in the knockout mice. However, the epithelial nitric oxide synthase isoform displayed no significant changes.
  
  
  CONCLUSIONS
  These data suggest the potential involvement of an abnormal nitric oxide metabolism in the pathogenesis of the fragile X syndrome.
authors.affiliation: UGC Salud Mental, Hospital Regional Universitario de Malaga, IBIMA Institute, University of Malaga, Research Laboratory, Hospital Civil, Pabellon 5, Sotano, 29009 Malaga, Spain; Plant Reproductive Biology Group, Department of Biochemistry, Cell and Molecular Biology of Plants, Estacion Experimental del Zaidin, Spanish Council for Scientific Research (CSIC), Profesor Albareda, 1, 18160 Granada, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Lima-Cabello
authors.affiliation: UGC Salud Mental, Hospital Regional Universitario de Malaga, IBIMA Institute, University of Malaga, Research Laboratory, Hospital Civil, Pabellon 5, Sotano, 29009 Malaga, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Garcia-Guirado
authors.affiliation: UGC Pediatria, Seccion Neuropediatria, Hospital Regional Universitario Malaga, Hospital Materno-Infantil, Planta Baja, 29009 Malaga, Spain.
authors.forename: Rocio
authors.initials: R
authors.lastname: Calvo-Medina
authors.affiliation: UGC Endocrinologia y Nutricion, Instituto de Investigacion Biomedica de Malaga (IBIMA), Hospital Regional Universitario de Malaga, Universidad de Malaga, CIBER de Fisiopatología de la Obesidad y Nutricion (CIBERobn), Instituto de Salud Carlos III (ISCIII), Hospital Civil, Pabellon 5 Sotano, 29009 Malaga, Spain.
authors.forename: Rajaa
authors.initials: R
authors.lastname: el Bekay
authors.affiliation: UGC Salud Mental, Hospital Regional Universitario de Malaga, IBIMA Institute, University of Malaga, Research Laboratory, Hospital Civil, Pabellon 5, Sotano, 29009 Malaga, Spain; Departamento de Salud Publica y Psiquiatria, Universidad de Malaga, Teatinos, 29010 Malaga, Spain.
authors.forename: Lucia
authors.initials: L
authors.lastname: Perez-Costillas
authors.affiliation: UGC Salud Mental, Hospital Regional Universitario de Malaga, IBIMA Institute, University of Malaga, Research Laboratory, Hospital Civil, Pabellon 5, Sotano, 29009 Malaga, Spain.
authors.forename: Carolina
authors.initials: C
authors.lastname: Quintero-Navarro
authors.affiliation: UGC Salud Mental, Hospital Regional Universitario de Malaga, IBIMA Institute, University of Malaga, Research Laboratory, Hospital Civil, Pabellon 5, Sotano, 29009 Malaga, Spain.
authors.forename: Lourdes
authors.initials: L
authors.lastname: Sanchez-Salido
authors.affiliation: UGC Salud Mental, Hospital Regional Universitario de Malaga, IBIMA Institute, University of Malaga, Research Laboratory, Hospital Civil, Pabellon 5, Sotano, 29009 Malaga, Spain.
authors.forename: Yolanda
authors.identifier: 0000-0003-2384-8349
authors.initials: Y
authors.lastname: de Diego-Otero
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D003600:Cytosol / Q000378:metabolism; D004195:Disease Models, Animal; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000378:metabolism; D005600:Fragile X Syndrome / Q000378:metabolism* / Q000473:pathology*; D008607:Intellectual Disability / Q000378:metabolism* / Q000473:pathology*; D007527:Isoenzymes / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D018345:Mice, Knockout; D008954:Models, Biological; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D046509:Tissue Culture Techniques; D051996:Transcription Factor RelA / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; D007527:Isoenzymes; D008070:Lipopolysaccharides; D009566:Nitrates; D009569:Nitric Oxide; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D009573:Nitrites; D012333:RNA, Messenger; D051996:Transcription Factor RelA; D014443:Tyrosine; C497684:Fmr1 protein, mouse; C002744:3-nitrotyrosine