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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
Supervisors
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.
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.
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.
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.
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