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. © 2014 Claudio De Felice et al.

Inflammatory lung disease in Rett syndrome / Felicec, De; Rossim, ; Leoncinis, ; Chiscig, ; Signorinic, ; Lonettig, ; Vannuccinil, ; Spinad, ; Ginoria, ; Iaconai, ; Cortelazzoa, ; Pecorellia, ; Valacchig, ; Ciccolil, ; Pizzorussot, ; Hayekj,. - In: MEDIATORS OF INFLAMMATION. - ISSN 0962-9351. - STAMPA. - 2014:(2014), pp. 0-0. [10.1155/2014/560120]

Inflammatory lung disease in Rett syndrome

LEONCINI, SABINA;LONETTI, GIUSEPPINA;PIZZORUSSO, TOMMASO;
2014

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. © 2014 Claudio De Felice et al.
2014
2014
0
0
Felicec, De; Rossim, ; Leoncinis, ; Chiscig, ; Signorinic, ; Lonettig, ; Vannuccinil, ; Spinad, ; Ginoria, ; Iaconai, ; Cortelazzoa, ; Pecorellia, ; V...espandi
File in questo prodotto:
File Dimensione Formato  
de felice.pdf

accesso aperto

Descrizione: articolo principale
Tipologia: Pdf editoriale (Version of record)
Licenza: Creative commons
Dimensione 2.79 MB
Formato Adobe PDF
2.79 MB Adobe PDF

I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1016041
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 25
  • ???jsp.display-item.citation.isi??? 22
social impact