Enhanced markers of oxidative stress, altered antioxidants and NADPH-oxidase activation in brains from Fragile X mental retardation 1-deficient mice, a pathological model for Fragile X syndrome.
Fragile X syndrome is the most common form of inherited mental retardation in humans. It originates from the loss of expression of the Fragile X mental retardation 1 (FMR1) gene, which results in the absence of the Fragile X mental retardation protein. However, the biochemical mechanisms involved in the pathological phenotype are mostly unknown. The availability of the FMR1-knockout mouse model offers an excellent model system in which to study the biochemical alterations related to brain abnormalities in the syndrome. We show for the first time that brains from Fmr1-knockout mice, a validated model for the syndrome, display higher levels of reactive oxygen species, nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase activation, lipid peroxidation and protein oxidation than brains from wild-type mice. Furthermore, the antioxidant system is deficient in Fmr1-knockout mice, as shown by altered levels of components of the glutathione system. FMR1-knockout mice lacking Fragile X mental retardation protein were compared with congenic FVB129 wild-type controls. Our results support the hypothesis that the lack of Fragile X mental retardation protein function leads to a moderate increase of the oxidative stress status in the brain that may contribute to the pathophysiology of the Fragile X syndrome.
el Bekay
Rajaa
R
Research Laboratory, Fundación IMABIS-Hospital Carlos Haya, Hospital Civil, Pabellón 5 Sótano, E-29009 Málaga, Spain.
Romero-Zerbo
Yanina
Y
Decara
Juan
J
Sanchez-Salido
Lourdes
L
Del Arco-Herrera
Ignacio
I
Rodríguez-de Fonseca
Fernando
F
de Diego-Otero
Yolanda
Y
D000367:Age Factors; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001921:Brain / Q000201:enzymology*; D004195:Disease Models, Animal; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D005600:Fragile X Syndrome / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D006861:Hydrogen Peroxide / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009249:NADP / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D010088:Oxidoreductases / Q000378:metabolism*; D050050:Protein Carbonylation / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D000975:Antioxidants; D051860:Fragile X Messenger Ribonucleoprotein 1; D006861:Hydrogen Peroxide; D009249:NADP; D010088:Oxidoreductases; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; C497684:Fmr1 protein, mouse