- Reversal of neurobehavioral social deficits in dystrophic mice using inhibitors of phosphodiesterases PDE5A and PDE9A.
Reversal of neurobehavioral social deficits in dystrophic mice using inhibitors of phosphodiesterases PDE5A and PDE9A.
Translational psychiatry (2016-09-28)
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
PMID27676442
摘要
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.