Rescue of fragile X syndrome phenotypes in Fmr1 KO mice by a BKCa channel opener molecule.

Abstract : Background:Fragile X Syndrome (FXS) is the most common form of inherited intellectual disability and is alsoassociated with autism spectrum disorders. Previous studies implicated BKCa channels in the neuropathogenesisof FXS, but the main question was whether pharmacological BKCa stimulation would be able to rescue FXSneurobehavioral phenotypes.Methods and results:We used a selective BKCa channel opener molecule (BMS-204352) to address this issue inFmr1KO mice, modeling the FXS pathophysiology.In vitro, acute BMS-204352 treatment (10μM) restored theabnormal dendritic spine phenotype.In vivo,a single injection of BMS-204352 (2 mg/kg) rescued the hippocampalglutamate homeostasis and the behavioral phenotype. Indeed, disturbances in social recognition and interaction,non-social anxiety, and spatial memory were corrected by BMS-204352 inFmr1KO mice.Conclusion:These results demonstrate that the BKCa channel is a new therapeutic target for FXS. We show thatBMS-204352 rescues a broad spectrum of behavioral impairments (social, emotional and cognitive) in an animalmodel of FXS. This pharmacological molecule might open new ways for FXS therapy.
Document type :
Journal articles
Complete list of metadatas

Cited literature [57 references]  Display  Hide  Download
Contributor : Delphine Autard <>
Submitted on : Tuesday, December 2, 2014 - 12:19:07 PM
Last modification on : Monday, March 25, 2019 - 5:32:08 PM
Long-term archiving on : Tuesday, March 3, 2015 - 1:12:34 PM


Publisher files allowed on an open archive


  • HAL Id : inserm-01089760, version 1
  • PUBMED : 25079250


Betty Hébert, Susanna Pietropaolo, Sandra Même, Béatrice Laudier, Anthony Laugeray, et al.. Rescue of fragile X syndrome phenotypes in Fmr1 KO mice by a BKCa channel opener molecule.. Orphanet Journal of Rare Diseases, BioMed Central, 2013, pp.124. ⟨inserm-01089760⟩



Record views


Files downloads