Oxidative brain damage in Mecp2-mutant murine models of Rett syndrome
| العنوان: | Oxidative brain damage in Mecp2-mutant murine models of Rett syndrome |
|---|---|
| المؤلفون: | Claudio De Felice, Thierry Durand, Francesco Scalabrì, Silvia Leoncini, Stefania Filosa, Lucia Ciccoli, Jacky Guy, Floriana Della Ragione, Alexandre Guy, Camille Oger, Bianca De Filippis, Jean-Marie Galano, Laura Ricceri, Joussef Hayek, Giovanni Laviola, Giuseppe Valacchi, Cinzia Signorini, Federico Marracino, Giuseppe Belmonte, Michele Madonna, Maurizio D'Esposito, Alessandra Pecorelli, Valérie Bultel-Poncé |
| المساهمون: | Neonatal Intensive Care Unit, Azienda Ospedaliera Universitaria Senese, Institute of Genetics and Biophysics Adriano Buzzati-Traverso (IGB), Consiglio Nazionale delle Ricerche [Roma] (CNR), Istituto Neurologico Mediterraneo Neuromed (IRCCS), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Child Neuropsychiatry Unit, Università degli Studi di Siena = University of Siena (UNISI), Department of Cell biology and Neuroscience (ISS), Istituto Superiore di Sanita [Rome], Department of Life Sciences and Biotechnologies, Università degli Studi di Ferrara (UniFE), Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM), Wellcome Trust Centre for Cell Biology, University of Edinburgh, Bando Salute 2009 project no. TR142 Italy, Italian Association for Rett Syndrome (AIR, call 2011), UE Initial Training Network project no. 238242 'DISCHROM', EPIGENOMICS flagship project EPIGEN, IRE-IFO (RF 2008) 'MECP2 phosphorylation and related kinase in Rett syndrome' to GL., Tuscany Region Italy |
| المصدر: | Neurobiology of Disease Neurobiology of Disease, Elsevier, 2014, 68, pp.66-77. ⟨10.1016/j.nbd.2014.04.006⟩ Neurobiology of Disease, Vol 68, Iss, Pp 66-77 (2014) Neurobiology of disease 68 (2014): 66–77. doi:10.1016/j.nbd.2014.04.006 info:cnr-pdr/source/autori:De Felice C.; Della Ragione F.; Signorini C.; Leoncini S.; Pecorelli A.; Ciccoli L.; Scalabri F.; Marracino F.; Madonna M.; Belmonte G.; Ricceri L.; De Filippis B.; Laviola G.; Valacchi G.; Durand T.; Galano J.-M.; Oger C.; Guy A.; Bultel-Ponce V.; Guy J.; Filosa S.; Hayek J.; D'Esposito M./titolo:Oxidative brain damage in Mecp2-mutant murine models of Rett syndrome/doi:10.1016%2Fj.nbd.2014.04.006/rivista:Neurobiology of disease/anno:2014/pagina_da:66/pagina_a:77/intervallo_pagine:66–77/volume:68 |
| بيانات النشر: | Academic Press, 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Male, IsoPs, isoprostanes, Methyl-CpG-Binding Protein 2, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, DHA, docosahexaenoic acid, Isoprostanes, medicine.disease_cause, Mecp2 stop/y, Lox/stop pre-symptomatic hemizygous mice, Pathogenesis, F4-NeuroPs, F4-neuroprostanes, Nestin, Mice, 0302 clinical medicine, Neurodevelopmental disorder, Rett syndrome, Mecp2 308/x, symptomatic Mecp2 308-mutated females, Mecp2 stop/y NestinCre, rescued Lox/stop mice (Mecp2 reactivated in the nervous tissue), CRE, Cre-Recombinase, wt-Cre, wild type expressing Cre recombinase, Genetics, 0303 health sciences, Mutation, Arachidonic Acid, Mecp2, methyl-CpG-binding protein 2 — mouse protein, 4-HNE PAs, 4-HNE protein adducts, MECP2, methyl-CpG-binding protein 2 — human gene, 4-HNE PAs, 4-hydroxy-2-nonenal protein adducts, Neurology, OS, oxidative stress, BDNF, brain-derived neurotrophic factor, ASDs, autism spectrum disorders, F2-IsoPs, F2-isoprostanes, Female, wt, wild type, medicine.symptom, AdA, adrenic acid, medicine.medical_specialty, congenital, hereditary, and neonatal diseases and abnormalities, Docosahexaenoic Acids, PSV, Preserved Speech Variant, RTT, Rett syndrome, Lipid peroxidation, Mice, Transgenic, Brain damage, Biology, Murine models, Oxidative stress, Article, 4-HNE, 4-hydroxy-2-nonenal, Gas Chromatography-Mass Spectrometry, lcsh:RC321-571, MECP2, 03 medical and health sciences, ROS, reactive oxygen species, Internal medicine, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], mental disorders, medicine, ARA, arachidonic acid, NPBI, non-protein-bound iron, Animals, Neuroprostanes, MeCP2, methyl-CpG-binding protein 2 — human protein, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, 030304 developmental biology, Mecp2, methyl-CpG-binding protein 2 — mouse gene, Aldehydes, Analysis of Variance, F2-dihomo-IsoPs, F2-dihomo-isoprostanes, PUFAs, polyunsaturated fatty acids, Wild type, medicine.disease, nervous system diseases, Mice, Inbred C57BL, Disease Models, Animal, Oxidative Stress, Endocrinology, AUs, arbitrary units, Brain Injuries, Mecp2 308/y, symptomatic Mecp2 308-mutated hemizygous males, 030217 neurology & neurosurgery, Mecp2 −/y, hemizygous null mice |
| الوصف: | Rett syndrome (RTT) is a rare neurodevelopmental disorder affecting almost exclusively females, caused in the overwhelming majority of the cases by loss-of-function mutations in the gene encoding methyl-CpG binding protein 2 (MECP2). High circulating levels of oxidative stress (OS) markers in patients suggest the involvement of OS in the RTT pathogenesis. To investigate the occurrence of oxidative brain damage in Mecp2 mutant mouse models, several OS markers were evaluated in whole brains of Mecp2-null (pre-symptomatic, symptomatic, and rescued) and Mecp2-308 mutated (pre-symptomatic and symptomatic) mice, and compared to those of wild type littermates. Selected OS markers included non-protein-bound iron, isoprostanes (F2-isoprostanes, F4-neuroprostanes, F2-dihomo-isoprostanes) and 4-hydroxy-2-nonenal protein adducts. Our findings indicate that oxidative brain damage 1) occurs in both Mecp2-null (both −/y and stop/y) and Mecp2-308 (both 308/y males and 308/+ females) mouse models of RTT; 2) precedes the onset of symptoms in both Mecp2-null and Mecp2-308 models; and 3) is rescued by Mecp2 brain specific gene reactivation. Our data provide direct evidence of the link between Mecp2 deficiency, oxidative stress and RTT pathology, as demonstrated by the rescue of the brain oxidative homeostasis following brain-specifically Mecp2-reactivated mice. The present study indicates that oxidative brain damage is a previously unrecognized hallmark feature of murine RTT, and suggests that Mecp2 is involved in the protection of the brain from oxidative stress. Highlights • Oxidative damage is demonstrated in the brain, and more specifically in the neurons, of Mecp2 mutant mouse models. • A direct evidence between enhanced oxidative stress and Mecp2 deficiency is provided. • Oxidative damage precedes the behavioral abnormalities in Mecp2 mutant mice. • Mecp2 is likely involved in the protection of the brain from oxidative stress. |
| اللغة: | English |
| تدمد: | 1095-953X 0969-9961 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7a02b3097fee569bc3aeeeef210ad36aTest http://europepmc.org/articles/PMC4076513Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....7a02b3097fee569bc3aeeeef210ad36a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1095953X 09699961 |
|---|