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Tesi etd-04262012-182452


Thesis type
Tesi di dottorato di ricerca
Author
PANIGHINI, ANNA
URN
etd-04262012-182452
Title
Vascular dysfunction in a mouse model of Rett Syndrome and effects of Curcumin treatment
Settore scientifico disciplinare
BIO/11
Corso di studi
NEUROBIOLOGIA E CLINICA DEI DISTURBI AFFETTIVI
Commissione
tutor Prof. Martini, Claudia
relatore Dott. Costa, Mario
Parole chiave
  • vascular endothelium
  • Rett Syndrome
  • Curcumin
Data inizio appello
08/06/2012;
Consultabilità
completa
Riassunto analitico
Mutations in the coding sequence of the X-linked gene MeCP2 (Methyl CpG–binding protein), are present in around 80% of patients with Rett Syndrome, a common cause of mental retardation in female and to date without any effective pharmacological treatment. A relevant, and so far unexplored feature of RTT patients is a marked reduction in peripheral circulation.<br>To investigate the relationship between loss of MeCP2 and this clinical aspect, we used a MeCP2 null mouse model, male (MeCP2y/-) and female (MeCP2+/-), for functional, pharmacological and behavioural studies. The functional studies performed on dissected branches of mesenteric arterial tree mounted on glass microcannule in a pressurized myograph, demonstrated a dramatic endothelial-dependent vascular reactivity impairment in MeCP2+/- compared to control littermate. The mesenteric arteriole preincubation with NOS inhibitors or ascorbic acid indicate a decrease Nitric Oxide (NO) availability and the increased presence of Reactive Oxygen Species (ROS). Consistently, the RTT mouse model exhibited a decreased expression in both mRNA and peptide eNOS in the arterioles and a higher systemic oxidative level. MeCP2 knockout mice show stereotyped movements and less resting time when compared to control littermates.<br>Chronic curcumin treatment of female MeCP2+/- mice was able to reverse this vascular phenotype and ameliorate the mouse RTT behavioural symptomatology by decreasing stereotyped movements and by increasing resting time. <br>These data indicate that in the absence of MeCP2 peripheral circulation is impaired by an altered vascular reactivity and decreased arteriolar eNOS expression and NO production. Further, they provide a physiological/molecular rational for the use of curcumin as a treatment to improve the health of RTT patients.<br>
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