Sildenafil protects against 3-nitropropionic acid neurotoxicity through the modulation of calpain, CREB, and BDNF

Neurobiology of Disease
E PuertaN Aguirre

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.

References

Sep 29, 1999·Proceedings of the National Academy of Sciences of the United States of America·A KazantsevD Housman
Apr 26, 2000·Behavioural Pharmacology·C M Baratti, M M Boccia
May 29, 2000·Brain Research·I FerrerT Ribalta
Feb 9, 2002·European Journal of Pharmacology·Jos PrickaertsArjan Blokland
Nov 2, 2002·Stroke; a Journal of Cerebral Circulation·Ruilan ZhangMichael Chopp
Apr 30, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Zachary C BaquetKevin R Jones
May 4, 2004·Molecular Therapy : the Journal of the American Society of Gene Therapy·Adrian P KellsBronwen Connor
Apr 9, 2005·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Lei WangMichael Chopp
Sep 14, 2006·Pharmacological Reviews·Andrew T Bender, Joseph A Beavo
Dec 23, 2006·Neurobiology of Disease·Zena DeMarchFrancesca Romana Fusco
Sep 22, 2007·The Journal of Clinical Investigation·Sung-Rae ChoSteven A Goldman
Apr 18, 2008·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Guangliang DingMichael Chopp
Aug 30, 2008·Neuropsychiatric Disease and Treatment·Daniela PuzzoAgostino Palmeri
Sep 3, 2008·The Journal of Sexual Medicine·Taymour Mostafa
Nov 28, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Catherine M CowanLynn A Raymond
Jun 6, 2009·Nature Reviews. Neurology·Chiara Zuccato, Elena Cattaneo
Jun 27, 2009·Neurobiology of Disease·Sandra AlmeidaA Cristina Rego
Sep 5, 2009·The Journal of Pharmacology and Experimental Therapeutics·Frank S MennitiSeth P Finklestein

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Citations

Apr 30, 2013·Journal of Molecular Neuroscience : MN·Dwayne BrownYousef Tizabi
Mar 15, 2012·Molecular Neurobiology·Ruhi S DeshmukhIpsita Roy
Aug 29, 2012·Journal of Applied Microbiology·I-H JungD-H Kim
Sep 20, 2011·Phytotherapy Research : PTR·Eun-Ha JohDong-Hyun Kim
Jun 2, 2011·British Journal of Pharmacology·M Cuadrado-TejedorA García-Osta
Oct 12, 2013·Neurobiology of Aging·Daniela PuzzoAgostino Palmeri
May 7, 2011·Neurobiology of Aging·Lourdes OrejanaNorberto Aguirre
Jul 27, 2014·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Lourdes OrejanaElena Puerta
Nov 28, 2012·Neurochemistry International·Judith PradoAgustina García
Jul 16, 2013·European Journal of Pharmacology·Sorabh SharmaPyare Lal Sharma
May 24, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Susann SchröderPeter Brust
Aug 17, 2016·Brain Pathology·Mar PuigdellívolEsther Pérez-Navarro
Mar 25, 2017·International Journal of Molecular Sciences·Eric P KnottDamien D Pearse
Mar 4, 2018·CNS Neuroscience & Therapeutics·Antonella Cardinale, Francesca R Fusco
Apr 20, 2018·Expert Opinion on Therapeutic Targets·Ana SaavedraJordi Alberch
Jan 20, 2011·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Tina HistingMichael D Menger
Aug 10, 2019·Frontiers in Immunology·Melissa SchepersTim Vanmierlo
Mar 10, 2017·International Journal of Molecular Sciences·Shang-Der ChenDing-I Yang
Dec 26, 2016·Naunyn-Schmiedeberg's Archives of Pharmacology·Katarzyna SocałaPiotr Wlaź
Sep 20, 2019·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Seyed Mohammad NabaviMohammad Hosein Farzaei
Feb 15, 2020·Journal of Affective Disorders·Eduardo Duarte-SilvaChristina Peixoto
Aug 16, 2019·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Edward J CalabreseRehana K Leak
Jun 23, 2021·Movement Disorders : Official Journal of the Movement Disorder Society·Roberto ErroKailash P Bhatia
Aug 18, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·YuFei HeYing Xie

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