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Reversal of neurobehavioral social deficits in dystrophic mice using inhibitors of phosphodiesterases PDE5A and PDE9A

Duchenne muscular dystrophy is caused by mutations in the DYSTROPHIN gene. Although primarily associated with muscle wasting, a significant portion of patients (approximately 25%) are also diagnosed with autism spectrum disorder. We describe social behavioral deficits in dystrophin-deficient mice an...

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Autores principales: Alexander, M S, Gasperini, M J, Tsai, P T, Gibbs, D E, Spinazzola, J M, Marshall, J L, Feyder, M J, Pletcher, M T, Chekler, E L P, Morris, C A, Sahin, M, Harms, J F, Schmidt, C J, Kleiman, R J, Kunkel, L M
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5048211/
https://www.ncbi.nlm.nih.gov/pubmed/27676442
http://dx.doi.org/10.1038/tp.2016.174
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author Alexander, M S
Gasperini, M J
Tsai, P T
Gibbs, D E
Spinazzola, J M
Marshall, J L
Feyder, M J
Pletcher, M T
Chekler, E L P
Morris, C A
Sahin, M
Harms, J F
Schmidt, C J
Kleiman, R J
Kunkel, L M
author_facet Alexander, M S
Gasperini, M J
Tsai, P T
Gibbs, D E
Spinazzola, J M
Marshall, J L
Feyder, M J
Pletcher, M T
Chekler, E L P
Morris, C A
Sahin, M
Harms, J F
Schmidt, C J
Kleiman, R J
Kunkel, L M
author_sort Alexander, M S
collection PubMed
description Duchenne muscular dystrophy is caused by mutations in the DYSTROPHIN gene. Although primarily associated with muscle wasting, a significant portion of patients (approximately 25%) are also diagnosed with autism spectrum disorder. We describe social behavioral deficits in dystrophin-deficient mice and present evidence of cerebellar deficits in cGMP production. We demonstrate therapeutic potential for selective inhibitors of the cGMP-specific PDE5A and PDE9A enzymes to restore social behaviors in dystrophin-deficient mice.
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spelling pubmed-50482112016-10-18 Reversal of neurobehavioral social deficits in dystrophic mice using inhibitors of phosphodiesterases PDE5A and PDE9A Alexander, M S Gasperini, M J Tsai, P T Gibbs, D E Spinazzola, J M Marshall, J L Feyder, M J Pletcher, M T Chekler, E L P Morris, C A Sahin, M Harms, J F Schmidt, C J Kleiman, R J Kunkel, L M Transl Psychiatry Original Article Duchenne muscular dystrophy is caused by mutations in the DYSTROPHIN gene. Although primarily associated with muscle wasting, a significant portion of patients (approximately 25%) are also diagnosed with autism spectrum disorder. We describe social behavioral deficits in dystrophin-deficient mice and present evidence of cerebellar deficits in cGMP production. We demonstrate therapeutic potential for selective inhibitors of the cGMP-specific PDE5A and PDE9A enzymes to restore social behaviors in dystrophin-deficient mice. Nature Publishing Group 2016-09 2016-09-27 /pmc/articles/PMC5048211/ /pubmed/27676442 http://dx.doi.org/10.1038/tp.2016.174 Text en Copyright © 2016 The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Original Article
Alexander, M S
Gasperini, M J
Tsai, P T
Gibbs, D E
Spinazzola, J M
Marshall, J L
Feyder, M J
Pletcher, M T
Chekler, E L P
Morris, C A
Sahin, M
Harms, J F
Schmidt, C J
Kleiman, R J
Kunkel, L M
Reversal of neurobehavioral social deficits in dystrophic mice using inhibitors of phosphodiesterases PDE5A and PDE9A
title Reversal of neurobehavioral social deficits in dystrophic mice using inhibitors of phosphodiesterases PDE5A and PDE9A
title_full Reversal of neurobehavioral social deficits in dystrophic mice using inhibitors of phosphodiesterases PDE5A and PDE9A
title_fullStr Reversal of neurobehavioral social deficits in dystrophic mice using inhibitors of phosphodiesterases PDE5A and PDE9A
title_full_unstemmed Reversal of neurobehavioral social deficits in dystrophic mice using inhibitors of phosphodiesterases PDE5A and PDE9A
title_short Reversal of neurobehavioral social deficits in dystrophic mice using inhibitors of phosphodiesterases PDE5A and PDE9A
title_sort reversal of neurobehavioral social deficits in dystrophic mice using inhibitors of phosphodiesterases pde5a and pde9a
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5048211/
https://www.ncbi.nlm.nih.gov/pubmed/27676442
http://dx.doi.org/10.1038/tp.2016.174
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