title: F(2)-Dihomo-isoprostanes and brain white matter damage in stage 1 Rett syndrome.
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.
authors.affiliation: Institut des Biomolécules Max Mousseron (IBMM), UMR 5247, CNRS/UM1/UM2, Montpellier, France. Thierry.Durand@univ-montp1.fr
authors.forename: Thierry
authors.initials: T
authors.lastname: Durand
authors.forename: Claudio
authors.initials: C
authors.lastname: De Felice
authors.forename: Cinzia
authors.initials: C
authors.lastname: Signorini
authors.forename: Camille
authors.initials: C
authors.lastname: Oger
authors.forename: Valérie
authors.initials: V
authors.lastname: Bultel-Poncé
authors.forename: Alexandre
authors.initials: A
authors.lastname: Guy
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Galano
authors.forename: Silvia
authors.initials: S
authors.lastname: Leoncini
authors.forename: Lucia
authors.initials: L
authors.lastname: Ciccoli
authors.forename: Alessandra
authors.initials: A
authors.lastname: Pecorelli
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Valacchi
authors.forename: Joussef
authors.initials: J
authors.lastname: Hayek
mesh_terms: D015415:Biomarkers / Q000097:blood*; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004883:Erucic Acids / Q000737:chemistry / Q000378:metabolism; D028441:F2-Isoprostanes / Q000008:administration & dosage / Q000097:blood / Q000138:chemical synthesis / Q000493:pharmacokinetics; D005231:Fatty Acids, Unsaturated; D006801:Humans; D056784:Leukoencephalopathies / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics / Q000378:metabolism; D009186:Myelin Sheath / Q000737:chemistry / Q000473:pathology; D018384:Oxidative Stress; D015518:Rett Syndrome / Q000097:blood / Q000175:diagnosis / Q000473:pathology
chemical_list: D015415:Biomarkers; D004883:Erucic Acids; D028441:F2-Isoprostanes; D005231:Fatty Acids, Unsaturated; C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2; C011395:adrenic acid