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

Research output: Contribution to journalArticle

7 Scopus citations

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 languageEnglish (US)
Article numbere901
JournalTranslational Psychiatry
Volume6
Issue number9
DOIs
StatePublished - 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), [e901]. https://doi.org/10.1038/tp.2016.174