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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
Author(s) -
El Bekay Rajaa,
RomeroZerbo Yanina,
Decara Juan,
SanchezSalido Lourdes,
Del ArcoHerrera Ignacio,
Rodríguezde Fonseca Fernando,
De DiegoOtero Yolanda
Publication year - 2007
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2007.05939.x
Subject(s) - fragile x syndrome , fmr1 , knockout mouse , oxidative stress , nicotinamide adenine dinucleotide phosphate , nadph oxidase , reactive oxygen species , biology , endocrinology , chemistry , biochemistry , oxidase test , fragile x , genetics , gene , enzyme
Abstract 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.