1. F(2)-Dihomo-isoprostanes and brain white matter damage in stage 1 Rett syndrome.
- Author
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Durand T, De Felice C, Signorini C, Oger C, Bultel-Poncé V, Guy A, Galano JM, Leoncini S, Ciccoli L, Pecorelli A, Valacchi G, and Hayek J
- Subjects
- Erucic Acids chemistry, Erucic Acids metabolism, Fatty Acids, Unsaturated, Humans, Leukoencephalopathies drug therapy, Leukoencephalopathies metabolism, Leukoencephalopathies pathology, Lipid Peroxidation drug effects, Myelin Sheath chemistry, Myelin Sheath pathology, Oxidative Stress, Biomarkers blood, Brain drug effects, Brain metabolism, Brain pathology, F2-Isoprostanes administration & dosage, F2-Isoprostanes blood, F2-Isoprostanes chemical synthesis, F2-Isoprostanes pharmacokinetics, Methyl-CpG-Binding Protein 2 genetics, Methyl-CpG-Binding Protein 2 metabolism, Rett Syndrome blood, Rett Syndrome diagnosis, Rett Syndrome pathology
- Abstract
Oxidative damage has been reported in Rett syndrome (RTT), a pervasive development disorder mainly caused up to 95% of cases by mutations in the X-linked methyl-CpG binding protein 2 (MeCP2) gene. We have recently synthesized F(2)-Dihomo-isoprostanes (F(2)-Dihomo-IsoP), peroxidation products from adrenic acid (C22:4 n - 6, AdA), a known component of myelin, and tested the potential value of F(2)-Dihomo-IsoPs as a novel disease marker and its relationship with clinical presentation, and disease progression. F(2)-Dihomo-IsoPs were determined by a gas chromatography/negative ion chemical ionization tandem mass spectrometry. The ent-7(RS)-F(2t)-Dihomo-IsoP and 17-F(2t)-Dihomo-IsoP were used as reference standards. The measured ions were the product ions at m/z 327 derived from the [M - 181](-) precursor ions (m/z 597) produced from both the derivatized ent-7(RS)-F(2t)-Dihomo-IsoP and 17-F(2t)-Dihomo-IsoP. Average plasma F(2)-Dihomo-IsoP levels in RTT were about 1 order of magnitude higher than in healthy controls, being higher in typical RTT as compared to RTT variants, with a remarkable increase of about 2 orders of magnitude in patients at the earliest stage of the disease followed by a steady decrease during the natural clinical progression. These data indicate for the first time that quantification of F(2)-Dihomo-IsoPs in plasma represents an early marker of the disease and may provide a better understanding of the pathogenic mechanisms behind the neurological regression in patients with RTT., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)
- Published
- 2013
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