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Sildenafil protects against 3-nitropropionic acid neurotoxicity through the modulation of calpain, CREB, and BDNF.
Neurobiol Dis. 2010 May; 38(2):237-45.ND

Abstract

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.

Authors+Show Affiliations

Department of Pharmacology, School of Medicine, University of Navarra, Pamplona, Spain.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20109548

Citation

Puerta, Elena, et al. "Sildenafil Protects Against 3-nitropropionic Acid Neurotoxicity Through the Modulation of Calpain, CREB, and BDNF." Neurobiology of Disease, vol. 38, no. 2, 2010, pp. 237-45.
Puerta E, Hervias I, Barros-Miñones L, et al. Sildenafil protects against 3-nitropropionic acid neurotoxicity through the modulation of calpain, CREB, and BDNF. Neurobiol Dis. 2010;38(2):237-45.
Puerta, E., Hervias, I., Barros-Miñones, L., Jordan, J., Ricobaraza, A., Cuadrado-Tejedor, M., García-Osta, A., & Aguirre, N. (2010). Sildenafil protects against 3-nitropropionic acid neurotoxicity through the modulation of calpain, CREB, and BDNF. Neurobiology of Disease, 38(2), 237-45. https://doi.org/10.1016/j.nbd.2010.01.013
Puerta E, et al. Sildenafil Protects Against 3-nitropropionic Acid Neurotoxicity Through the Modulation of Calpain, CREB, and BDNF. Neurobiol Dis. 2010;38(2):237-45. PubMed PMID: 20109548.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sildenafil protects against 3-nitropropionic acid neurotoxicity through the modulation of calpain, CREB, and BDNF. AU - Puerta,Elena, AU - Hervias,Isabel, AU - Barros-Miñones,Lucía, AU - Jordan,Joaquin, AU - Ricobaraza,Ana, AU - Cuadrado-Tejedor,Mar, AU - García-Osta,Ana, AU - Aguirre,Norberto, Y1 - 2010/01/25/ PY - 2009/09/25/received PY - 2009/12/24/revised PY - 2010/01/17/accepted PY - 2010/1/30/entrez PY - 2010/1/30/pubmed PY - 2010/7/2/medline SP - 237 EP - 45 JF - Neurobiology of disease JO - Neurobiol Dis VL - 38 IS - 2 N2 - 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. SN - 1095-953X UR - https://www.unboundmedicine.com/medline/citation/20109548/Sildenafil_protects_against_3_nitropropionic_acid_neurotoxicity_through_the_modulation_of_calpain_CREB_and_BDNF_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0969-9961(10)00015-X DB - PRIME DP - Unbound Medicine ER -