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

M. S. Alexander; M. J. Gasperini; P. T. Tsai; D. E. Gibbs; J. M. Spinazzola; J. L. Marshall; M. J. Feyder; M. T. Pletcher; E. L.P. Chekler; C. A. Morris; M. Sahin; J. F. Harms; C. J. Schmidt; R. J. Kleiman; L. M. Kunkel

doi:10.1038/tp.2016.174

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

M. S. Alexander, M. J. Gasperini, P. T. Tsai, D. E. Gibbs, J. M. Spinazzola, J. L. Marshall, M. J. Feyder, M. T. Pletcher, E. L.P. Chekler, C. A. Morris, M. Sahin, J. F. Harms, C. J. Schmidt, R. J. Kleiman, L. M. Kunkel

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Abstract

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.

Original language	English (US)
Article number	e901
Journal	Translational psychiatry
Volume	6
Issue number	9
DOIs	https://doi.org/10.1038/tp.2016.174
State	Published - Sep 27 2016

ASJC Scopus subject areas

Psychiatry and Mental health
Cellular and Molecular Neuroscience
Biological Psychiatry

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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. (2016). Reversal of neurobehavioral social deficits in dystrophic mice using inhibitors of phosphodiesterases PDE5A and PDE9A. Translational psychiatry, 6(9), Article e901. https://doi.org/10.1038/tp.2016.174

Alexander, MS, Gasperini, MJ, Tsai, PT, Gibbs, DE, Spinazzola, JM, Marshall, JL, Feyder, MJ, Pletcher, MT, Chekler, ELP, Morris, CA, Sahin, M, Harms, JF, Schmidt, CJ, Kleiman, RJ & Kunkel, LM 2016, 'Reversal of neurobehavioral social deficits in dystrophic mice using inhibitors of phosphodiesterases PDE5A and PDE9A', Translational psychiatry, vol. 6, no. 9, e901. https://doi.org/10.1038/tp.2016.174

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abstract = "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.",

author = "Alexander, {M. S.} and Gasperini, {M. J.} and Tsai, {P. T.} and Gibbs, {D. E.} and Spinazzola, {J. M.} and Marshall, {J. L.} and Feyder, {M. J.} and Pletcher, {M. T.} and Chekler, {E. L.P.} and Morris, {C. A.} and M. Sahin and Harms, {J. F.} and Schmidt, {C. J.} and Kleiman, {R. J.} and Kunkel, {L. M.}",

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AU - Spinazzola, J. M.

AU - Marshall, J. L.

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AU - Pletcher, M. T.

AU - Chekler, E. L.P.

AU - Morris, C. A.

AU - Sahin, M.

AU - Harms, J. F.

AU - Schmidt, C. J.

AU - Kleiman, R. J.

AU - Kunkel, L. M.

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

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