Sildenafil protects against 3-nitropropionic acid neurotoxicity through the modulation of calpain, CREB and BDNF
In this study we tested whether phosphodiesterase 5 (PDE5) inhibitors, sildenafil and vardenafil, would afford protection against 3-nitropropionic acid (3NP), which produces striatal lesions that closely mimic some of the neuropathological features of Huntington's Disease (HD). The neurotoxin...
| Main Authors: | , , , , , , , |
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| Format: | info:eu-repo/semantics/article |
| Language: | eng |
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ACADEMIC PRESS INC ELSEVIER SCIENCE
2010
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| Subjects: | |
| Online Access: | https://hdl.handle.net/10171/12941 |
| _version_ | 1793400096392478720 |
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| author | Puerta, E. (Elena) Hervias, I. (Isabel) Barros-Miñones, L. (Lucía) Jordan, J. (Joaquín) Ricobaraza, A. (Ana) Cuadrado-Tejedor, M. (Mar) Garcia-Osta, A. (Ana) Aguirre, N. (Norberto) |
| author_facet | Puerta, E. (Elena) Hervias, I. (Isabel) Barros-Miñones, L. (Lucía) Jordan, J. (Joaquín) Ricobaraza, A. (Ana) Cuadrado-Tejedor, M. (Mar) Garcia-Osta, A. (Ana) Aguirre, N. (Norberto) |
| author_sort | Puerta, E. (Elena) |
| collection | DSpace |
| description | In this study we tested whether phosphodiesterase 5 (PDE5) inhibitors, sildenafil and vardenafil, would
afford protection against 3-nitropropionic acid (3NP), which produces striatal lesions that closely mimic
some of the neuropathological features of Huntington's Disease (HD). The neurotoxin was given over 5 days
by constant systemic infusion using osmotic minipumps. Animals treated with PDE5 inhibitors (sildenafil or
vardenafil) showed improved neurologic scores, reduced the loss of striatal DARPP-32 protein levels and
lesion volumes, and decreased calpain activation produced by 3NP. This protective effect was independent of
changes in 3NP-induced succinate dehydrogenase inhibition. Furthermore, striatal p-CREB levels along with
the expression of BDNF were significantly increased in sildenafil-treated rats. In summary, PDE5 inhibitors
protected against 3NP-induced striatal degeneration by reducing calpain activation and by promoting
survival pathways. These data encourage further evaluation of PDE5 inhibitors in transgenic mouse models
of HD. |
| format | info:eu-repo/semantics/article |
| id | oai:dadun.unav.edu:10171-12941 |
| institution | Universidad de Navarra |
| language | eng |
| publishDate | 2010 |
| publisher | ACADEMIC PRESS INC ELSEVIER SCIENCE |
| record_format | dspace |
| spelling | oai:dadun.unav.edu:10171-129412017-05-14T07:06:20Z Sildenafil protects against 3-nitropropionic acid neurotoxicity through the modulation of calpain, CREB and BDNF Puerta, E. (Elena) Hervias, I. (Isabel) Barros-Miñones, L. (Lucía) Jordan, J. (Joaquín) Ricobaraza, A. (Ana) Cuadrado-Tejedor, M. (Mar) Garcia-Osta, A. (Ana) Aguirre, N. (Norberto) 3-Nitropropionic acid BDNF Calpain CREB Excitotoxicity Huntington's disease Phosphodiesterase 5 Sildenafil Vardenafil In this study we tested whether phosphodiesterase 5 (PDE5) inhibitors, sildenafil and vardenafil, would afford protection against 3-nitropropionic acid (3NP), which produces striatal lesions that closely mimic some of the neuropathological features of Huntington's Disease (HD). The neurotoxin was given over 5 days by constant systemic infusion using osmotic minipumps. Animals treated with PDE5 inhibitors (sildenafil or vardenafil) showed improved neurologic scores, reduced the loss of striatal DARPP-32 protein levels and lesion volumes, and decreased calpain activation produced by 3NP. This protective effect was independent of changes in 3NP-induced succinate dehydrogenase inhibition. Furthermore, striatal p-CREB levels along with the expression of BDNF were significantly increased in sildenafil-treated rats. In summary, PDE5 inhibitors protected against 3NP-induced striatal degeneration by reducing calpain activation and by promoting survival pathways. These data encourage further evaluation of PDE5 inhibitors in transgenic mouse models of HD. 2010-09-23T13:50:09Z 2010-09-23T13:50:09Z 2010-05-02 info:eu-repo/semantics/article https://hdl.handle.net/10171/12941 eng info:eu-repo/semantics/closedAccess ACADEMIC PRESS INC ELSEVIER SCIENCE |
| spellingShingle | 3-Nitropropionic acid BDNF Calpain CREB Excitotoxicity Huntington's disease Phosphodiesterase 5 Sildenafil Vardenafil Puerta, E. (Elena) Hervias, I. (Isabel) Barros-Miñones, L. (Lucía) Jordan, J. (Joaquín) Ricobaraza, A. (Ana) Cuadrado-Tejedor, M. (Mar) Garcia-Osta, A. (Ana) Aguirre, N. (Norberto) Sildenafil protects against 3-nitropropionic acid neurotoxicity through the modulation of calpain, CREB and BDNF |
| title | Sildenafil protects against 3-nitropropionic acid neurotoxicity through the modulation of calpain, CREB and BDNF |
| title_full | Sildenafil protects against 3-nitropropionic acid neurotoxicity through the modulation of calpain, CREB and BDNF |
| title_fullStr | Sildenafil protects against 3-nitropropionic acid neurotoxicity through the modulation of calpain, CREB and BDNF |
| title_full_unstemmed | Sildenafil protects against 3-nitropropionic acid neurotoxicity through the modulation of calpain, CREB and BDNF |
| title_short | Sildenafil protects against 3-nitropropionic acid neurotoxicity through the modulation of calpain, CREB and BDNF |
| title_sort | sildenafil protects against 3-nitropropionic acid neurotoxicity through the modulation of calpain, creb and bdnf |
| topic | 3-Nitropropionic acid BDNF Calpain CREB Excitotoxicity Huntington's disease Phosphodiesterase 5 Sildenafil Vardenafil |
| url | https://hdl.handle.net/10171/12941 |
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