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Oxidative Medicine and Cellular Longevity
Volume 2014, Article ID 195935, 10 pages
Research Article

Redox Imbalance and Morphological Changes in Skin Fibroblasts in Typical Rett Syndrome

1Department of Molecular and Developmental Medicine, University of Siena, 53100 Siena, Italy
2Child Neuropsychiatry Unit, University Hospital Azienda Ospedaliera Universitaria Senese (AOUS), 53100 Siena, Italy
3Neonatal Intensive Care Unit, University Hospital AOUS, Policlinico “S. M. alle Scotte,” 53100 Siena, Italy
4Medical Genetics, University of Siena, 53100 Siena, Italy
5Department of Life Sciences, University of Siena, 53100 Siena, Italy
6Department of Medicine Surgery and Neuroscience, University of Siena, 53100 Siena, Italy
7Department of Life Science and Biotechnologies, University of Ferrara, 44121 Ferrara, Italy
8Institut des Biomolécules Max Mousseron (IBMM), UMR 5247-CNRS-UM I-UM II-ENSCM, BP 14491 34093, Montpellier Cedex 5, France
9Genetica Medica, Azienda Ospedaliera Universitaria Senese, 53100 Siena, Italy

Received 10 March 2014; Revised 9 May 2014; Accepted 12 May 2014; Published 29 May 2014

Academic Editor: Ozcan Erel

Copyright © 2014 Cinzia Signorini et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Evidence of oxidative stress has been reported in the blood of patients with Rett syndrome (RTT), a neurodevelopmental disorder mainly caused by mutations in the gene encoding the Methyl-CpG-binding protein 2. Little is known regarding the redox status in RTT cellular systems and its relationship with the morphological phenotype. In RTT patients (n = 16) we investigated four different oxidative stress markers, F2-Isoprostanes (F2-IsoPs), F4-Neuroprostanes (F4-NeuroPs), nonprotein bound iron (NPBI), and (4-HNE PAs), and glutathione in one of the most accessible cells, that is, skin fibroblasts, and searched for possible changes in cellular/intracellular structure and qualitative modifications of synthesized collagen. Significantly increased F4-NeuroPs (12-folds), F2-IsoPs (7.5-folds) NPBI (2.3-folds), 4-HNE PAs (1.48-folds), and GSSG (1.44-folds) were detected, with significantly decreased GSH (−43.6%) and GSH/GSSG ratio (−3.05 folds). A marked dilation of the rough endoplasmic reticulum cisternae, associated with several cytoplasmic multilamellar bodies, was detectable in RTT fibroblasts. Colocalization of collagen I and collagen III, as well as the percentage of type I collagen as derived by semiquantitative immunofluorescence staining analyses, appears to be significantly reduced in RTT cells. Our findings indicate the presence of a redox imbalance and previously unrecognized morphological skin fibroblast abnormalities in RTT patients.