Rescue of fragile X syndrome phenotypes in Fmr1KO mice by a BKCa channel opener molecule

• DOI: 10.1186/s13023-014-0124-6
• Publication Date: 2014-07-31T02:42:39Z
• Authors: Betty Hébert; Susanna Pietropaolo; Sandra Même; Béatrice Laudier; Anthony Laugeray; Nicolas Doisne; Angélique Quartier; Sandrine Lefeuvre; Laurence Got; Dominique Cahard; Frédéric Laumonnier; Wim E Crusio; Jacques Pichon; Arnaud Menuet; Olivier Perche; Sylvain Briault
• Keywords: Fragile X Syndrome; FMR1

Fragile X Syndrome (FXS) is the most common form of inherited intellectual disability and also associated with autism spectrum disorders. Previous studies implicated BKCa channels in neuropathogenesis FXS, but main question was whether pharmacological stimulation would be able to rescue FXS neurobehavioral phenotypes.We used a selective channel opener molecule (BMS-204352) address this issue Fmr1 KO mice, modeling pathophysiology. In vitro, acute BMS-204352 treatment (10 μM) restored abnormal dendritic spine phenotype. vivo, single injection (2 mg/kg) rescued hippocampal glutamate homeostasis behavioral Indeed, disturbances social recognition interaction, non-social anxiety, spatial memory were corrected by mice.These results demonstrate that new therapeutic target for FXS. We show rescues broad impairments (social, emotional cognitive) an animal model This might open ways therapy.