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Mediators Inflamm. 2014;2014:560120. doi: 10.1155/2014/560120. Epub 2014 Mar 17.

Inflammatory lung disease in Rett syndrome.

Author information

1
Neonatal Intensive Care Unit, University Hospital Azienda Ospedaliera Universitaria Senese (AOUS), Viale M. Bracci 16, 53100 Siena, Italy.
2
Respiratory Pathophysiology and Rehabilitation Unit, University Hospital, AOUS, Viale M. Bracci 16, 53100 Siena, Italy.
3
Department of Molecular and Developmental Medicine, University of Siena, Via A. Moro 2, 53100 Siena, Italy ; Child Neuropsychiatry Unit, University Hospital AOUS, Viale M. Bracci 16, 53100 Siena, Italy.
4
Department of Maxillofacial Surgery, University of Siena, Viale M. Bracci 16, 53100 Siena, Italy.
5
Department of Molecular and Developmental Medicine, University of Siena, Via A. Moro 2, 53100 Siena, Italy.
6
Institute of Neuroscience, CNR, Via G. Moruzzi 1, 56124 Pisa, Italy.
7
Pathology Unit, University Hospital AOUS, Viale M. Bracci 16, 53100 Siena, Italy.
8
Child Neuropsychiatry Unit, University Hospital AOUS, Viale M. Bracci 16, 53100 Siena, Italy ; Department of Medical Biotechnologies, University of Siena, Via A. Moro 2, 53100 Siena, Italy.
9
Department of Life Sciences and Biotechnology, University of Ferrara, Via Borsari 46, 44100 Ferrara, Italy.
10
Institute of Neuroscience, CNR, Via G. Moruzzi 1, 56124 Pisa, Italy ; Department of Neuroscience, Psychology, Drug Research and Child Health (Neurofarba), University of Florence, Area S. Salvi Pad. 26, 50135 Florence, Italy.
11
Child Neuropsychiatry Unit, University Hospital AOUS, Viale M. Bracci 16, 53100 Siena, Italy.

Abstract

Rett syndrome (RTT) is a pervasive neurodevelopmental disorder mainly linked to mutations in the gene encoding the methyl-CpG-binding protein 2 (MeCP2). Respiratory dysfunction, historically credited to brainstem immaturity, represents a major challenge in RTT. Our aim was to characterize the relationships between pulmonary gas exchange abnormality (GEA), upper airway obstruction, and redox status in patients with typical RTT (n = 228) and to examine lung histology in a Mecp2-null mouse model of the disease. GEA was detectable in ~80% (184/228) of patients versus ~18% of healthy controls, with "high" (39.8%) and "low" (34.8%) patterns dominating over "mixed" (19.6%) and "simple mismatch" (5.9%) types. Increased plasma levels of non-protein-bound iron (NPBI), F2-isoprostanes (F2-IsoPs), intraerythrocyte NPBI (IE-NPBI), and reduced and oxidized glutathione (i.e., GSH and GSSG) were evidenced in RTT with consequently decreased GSH/GSSG ratios. Apnea frequency/severity was positively correlated with IE-NPBI, F2-IsoPs, and GSSG and negatively with GSH/GSSG ratio. A diffuse inflammatory infiltrate of the terminal bronchioles and alveoli was evidenced in half of the examined Mecp2-mutant mice, well fitting with the radiological findings previously observed in RTT patients. Our findings indicate that GEA is a key feature of RTT and that terminal bronchioles are a likely major target of the disease.

PMID:
24757286
PMCID:
PMC3976920
DOI:
10.1155/2014/560120
[Indexed for MEDLINE]
Free PMC Article

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