Title |
Rescue of fragile X syndrome phenotypes in Fmr1KO mice by a BKCa channel opener molecule
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Published in |
Orphanet Journal of Rare Diseases, August 2014
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DOI | 10.1186/s13023-014-0124-6 |
Pubmed ID | |
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 |
Abstract |
BackgroundFragile 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.Methods and resultsWe 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 ¿M) 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.ConclusionThese 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. |
X Demographics
Geographical breakdown
Country | Count | As % |
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France | 1 | 33% |
Mexico | 1 | 33% |
Unknown | 1 | 33% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 3 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 120 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Bachelor | 18 | 15% |
Student > Ph. D. Student | 16 | 13% |
Student > Master | 16 | 13% |
Researcher | 14 | 12% |
Student > Doctoral Student | 8 | 7% |
Other | 16 | 13% |
Unknown | 32 | 27% |
Readers by discipline | Count | As % |
---|---|---|
Neuroscience | 30 | 25% |
Agricultural and Biological Sciences | 21 | 18% |
Psychology | 9 | 8% |
Medicine and Dentistry | 8 | 7% |
Biochemistry, Genetics and Molecular Biology | 7 | 6% |
Other | 12 | 10% |
Unknown | 33 | 28% |