Vascular dysfunction in a mouse model of Rett syndrome and effects of curcumin treatment.
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 featur...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2013-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0064863&type=printable |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850138252829261824 |
|---|---|
| author | Anna Panighini Emiliano Duranti Ferruccio Santini Margherita Maffei Tommaso Pizzorusso Niccola Funel Stefano Taddei Nunzia Bernardini Chiara Ippolito Agostino Virdis Mario Costa |
| author_facet | Anna Panighini Emiliano Duranti Ferruccio Santini Margherita Maffei Tommaso Pizzorusso Niccola Funel Stefano Taddei Nunzia Bernardini Chiara Ippolito Agostino Virdis Mario Costa |
| author_sort | Anna Panighini |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-66b1d478ce13446db2827ef5df0a2e7c |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-66b1d478ce13446db2827ef5df0a2e7c2025-08-20T02:30:38ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0185e6486310.1371/journal.pone.0064863Vascular dysfunction in a mouse model of Rett syndrome and effects of curcumin treatment.Anna PanighiniEmiliano DurantiFerruccio SantiniMargherita MaffeiTommaso PizzorussoNiccola FunelStefano TaddeiNunzia BernardiniChiara IppolitoAgostino VirdisMario CostaMutations 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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0064863&type=printable |
| spellingShingle | Anna Panighini Emiliano Duranti Ferruccio Santini Margherita Maffei Tommaso Pizzorusso Niccola Funel Stefano Taddei Nunzia Bernardini Chiara Ippolito Agostino Virdis Mario Costa Vascular dysfunction in a mouse model of Rett syndrome and effects of curcumin treatment. PLoS ONE |
| title | Vascular dysfunction in a mouse model of Rett syndrome and effects of curcumin treatment. |
| title_full | Vascular dysfunction in a mouse model of Rett syndrome and effects of curcumin treatment. |
| title_fullStr | Vascular dysfunction in a mouse model of Rett syndrome and effects of curcumin treatment. |
| title_full_unstemmed | Vascular dysfunction in a mouse model of Rett syndrome and effects of curcumin treatment. |
| title_short | Vascular dysfunction in a mouse model of Rett syndrome and effects of curcumin treatment. |
| title_sort | vascular dysfunction in a mouse model of rett syndrome and effects of curcumin treatment |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0064863&type=printable |
| work_keys_str_mv | AT annapanighini vasculardysfunctioninamousemodelofrettsyndromeandeffectsofcurcumintreatment AT emilianoduranti vasculardysfunctioninamousemodelofrettsyndromeandeffectsofcurcumintreatment AT ferrucciosantini vasculardysfunctioninamousemodelofrettsyndromeandeffectsofcurcumintreatment AT margheritamaffei vasculardysfunctioninamousemodelofrettsyndromeandeffectsofcurcumintreatment AT tommasopizzorusso vasculardysfunctioninamousemodelofrettsyndromeandeffectsofcurcumintreatment AT niccolafunel vasculardysfunctioninamousemodelofrettsyndromeandeffectsofcurcumintreatment AT stefanotaddei vasculardysfunctioninamousemodelofrettsyndromeandeffectsofcurcumintreatment AT nunziabernardini vasculardysfunctioninamousemodelofrettsyndromeandeffectsofcurcumintreatment AT chiaraippolito vasculardysfunctioninamousemodelofrettsyndromeandeffectsofcurcumintreatment AT agostinovirdis vasculardysfunctioninamousemodelofrettsyndromeandeffectsofcurcumintreatment AT mariocosta vasculardysfunctioninamousemodelofrettsyndromeandeffectsofcurcumintreatment |