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

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2016

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Nature Publishing Group
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Alexander, M. S., M. J. Gasperini, P. T. Tsai, D. E. Gibbs, J. M. Spinazzola, J. L. Marshall, M. J. Feyder, et al. 2016. “Reversal of neurobehavioral social deficits in dystrophic mice using inhibitors of phosphodiesterases PDE5A and PDE9A.” Translational Psychiatry 6 (9): e901. doi:10.1038/tp.2016.174. http://dx.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.

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