| First Author | Panighini A | Year | 2013 |
| Journal | PLoS One | Volume | 8 |
| Issue | 5 | Pages | e64863 |
| PubMed ID | 23705018 | Mgi Jnum | J:202120 |
| Mgi Id | MGI:5517512 | Doi | 10.1371/journal.pone.0064863 |
| Citation | Panighini A, et al. (2013) Vascular dysfunction in a mouse model of rett syndrome and effects of curcumin treatment. PLoS One 8(5):e64863 |
| abstractText | 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 intellectual disability 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 the MeCP2 null mouse model B6.129SF1-MeCP2tm1Jae for functional and pharmacological studies. Functional experiments were performed on isolated resistance mesenteric vessels, mounted on a pressurized myograph. Vessels from female MeCP2(+/-) mice show a reduced endothelium-dependent relaxation, due to a reduced Nitric Oxide (NO) availability secondary to an increased Reactive Oxygen Species (ROS) generation. Such functional aspects are associated with an intravascular increase in superoxide anion production, and a decreased vascular eNOS expression. These alterations are reversed by curcumin administration (5% (w/w) dietary curcumin for 21 days), which restores endothelial NO availability, decreases intravascular ROS production and normalizes vascular eNOS gene expression. In conclusion our findings highlight alterations in the vascular/endothelial system in the absence of a correct function of MeCP2, and uncover related cellular/molecular mechanisms that are rescued by an anti-oxidant treatment. |
