title: 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 also associated with autism spectrum disorders. Previous studies implicated BKCa channels in the neuropathogenesis of FXS, but the main question was whether pharmacological BKCa stimulation would be able to rescue FXS neurobehavioral phenotypes.
  
  
  RESULTS
  We used a selective BKCa channel opener molecule (BMS-204352) to address this issue in Fmr1 KO mice, modeling the FXS pathophysiology. In vitro, acute BMS-204352 treatment (10 μM) restored the abnormal dendritic spine phenotype. In vivo, a single injection of BMS-204352 (2 mg/kg) rescued the hippocampal glutamate homeostasis and the behavioral phenotype. Indeed, disturbances in social recognition and interaction, non-social anxiety, and spatial memory were corrected by BMS-204352 in Fmr1 KO mice.
  
  
  CONCLUSIONS
  These results demonstrate that the BKCa channel is a new therapeutic target for FXS. We show that BMS-204352 rescues a broad spectrum of behavioral impairments (social, emotional and cognitive) in an animal model of FXS. This pharmacological molecule might open new ways for FXS therapy.
authors: Betty
authors: B
authors: Hébert
authors: Susanna
authors: S
authors: Pietropaolo
authors: Sandra
authors: S
authors: Même
authors: Béatrice
authors: B
authors: Laudier
authors: Anthony
authors: A
authors: Laugeray
authors: Nicolas
authors: N
authors: Doisne
authors: Angélique
authors: A
authors: Quartier
authors: Sandrine
authors: S
authors: Lefeuvre
authors: Laurence
authors: L
authors: Got
authors: Dominique
authors: D
authors: Cahard
authors: Frédéric
authors: F
authors: Laumonnier
authors: Wim E
authors: WE
authors: Crusio
authors: Jacques
authors: J
authors: Pichon
authors: Arnaud
authors: A
authors: Menuet
authors: Olivier
authors: O
authors: Perche
authors: Sylvain
authors: S
authors: Briault
mesh_terms: D000818:Animals; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D005600:Fragile X Syndrome / Q000235:genetics / Q000517:prevention & control*; D006801:Humans; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; C497683:FMR1 protein, human; C494841:KCNMA1 protein, human