Multiple Drug Treatments That Increase cAMP Signaling Restore Long-Term Memory and Aberrant Signaling in Fragile X Syndrome Models.

Autor: Choi CH; McDonald Laboratory, Section of Molecular Cardiology, Departments of Medicine and Molecular Pharmacology, Albert Einstein College of Medicine, Yeshiva UniversityBronx, NY, USA; Department of Dermatology, Dermatology Clinic, Drexel University College of MedicinePhiladelphia, PA, USA; Jongens Laboratory, Department of Genetics, University of Pennsylvania School of MedicinePhiladelphia, PA, USA., Schoenfeld BP; McDonald Laboratory, Section of Molecular Cardiology, Departments of Medicine and Molecular Pharmacology, Albert Einstein College of Medicine, Yeshiva UniversityBronx, NY, USA; Jongens Laboratory, Department of Genetics, University of Pennsylvania School of MedicinePhiladelphia, PA, USA., Bell AJ; McDonald Laboratory, Section of Molecular Cardiology, Departments of Medicine and Molecular Pharmacology, Albert Einstein College of Medicine, Yeshiva UniversityBronx, NY, USA; Jongens Laboratory, Department of Genetics, University of Pennsylvania School of MedicinePhiladelphia, PA, USA., Hinchey J; McDonald Laboratory, Section of Molecular Cardiology, Departments of Medicine and Molecular Pharmacology, Albert Einstein College of Medicine, Yeshiva University Bronx, NY, USA., Rosenfelt C; Bolduc Laboratory, Department of Pediatrics, Center for Neuroscience, University of Alberta Edmonton, AB, Canada., Gertner MJ; Zukin Laboratory, Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Yeshiva University Bronx, NY, USA., Campbell SR; McDonald Laboratory, Section of Molecular Cardiology, Departments of Medicine and Molecular Pharmacology, Albert Einstein College of Medicine, Yeshiva University Bronx, NY, USA., Emerson D; Jongens Laboratory, Department of Genetics, University of Pennsylvania School of Medicine Philadelphia, PA, USA., Hinchey P; McDonald Laboratory, Section of Molecular Cardiology, Departments of Medicine and Molecular Pharmacology, Albert Einstein College of Medicine, Yeshiva University Bronx, NY, USA., Kollaros M; McDonald Laboratory, Section of Molecular Cardiology, Departments of Medicine and Molecular Pharmacology, Albert Einstein College of Medicine, Yeshiva University Bronx, NY, USA., Ferrick NJ; McDonald Laboratory, Section of Molecular Cardiology, Departments of Medicine and Molecular Pharmacology, Albert Einstein College of Medicine, Yeshiva UniversityBronx, NY, USA; Jongens Laboratory, Department of Genetics, University of Pennsylvania School of MedicinePhiladelphia, PA, USA., Chambers DB; Bolduc Laboratory, Department of Pediatrics, Center for Neuroscience, University of Alberta Edmonton, AB, Canada., Langer S; Bolduc Laboratory, Department of Pediatrics, Center for Neuroscience, University of Alberta Edmonton, AB, Canada., Sust S; Siegel Laboratory, Translational Neuroscience Program, Department of Psychiatry, University of Pennsylvania School of Medicine Philadelphia, PA, USA., Malik A; Jongens Laboratory, Department of Genetics, University of Pennsylvania School of Medicine Philadelphia, PA, USA., Terlizzi AM; McDonald Laboratory, Section of Molecular Cardiology, Departments of Medicine and Molecular Pharmacology, Albert Einstein College of Medicine, Yeshiva University Bronx, NY, USA., Liebelt DA; McDonald Laboratory, Section of Molecular Cardiology, Departments of Medicine and Molecular Pharmacology, Albert Einstein College of Medicine, Yeshiva University Bronx, NY, USA., Ferreiro D; McDonald Laboratory, Section of Molecular Cardiology, Departments of Medicine and Molecular Pharmacology, Albert Einstein College of Medicine, Yeshiva University Bronx, NY, USA., Sharma A; Zukin Laboratory, Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Yeshiva University Bronx, NY, USA., Koenigsberg E; McDonald Laboratory, Section of Molecular Cardiology, Departments of Medicine and Molecular Pharmacology, Albert Einstein College of Medicine, Yeshiva University Bronx, NY, USA., Choi RJ; McDonald Laboratory, Section of Molecular Cardiology, Departments of Medicine and Molecular Pharmacology, Albert Einstein College of Medicine, Yeshiva University Bronx, NY, USA., Louneva N; Arnold Laboratory, Department of Psychiatry, University of Pennsylvania School of Medicine Philadelphia, PA, USA., Arnold SE; Arnold Laboratory, Department of Psychiatry, University of Pennsylvania School of Medicine Philadelphia, PA, USA., Featherstone RE; Siegel Laboratory, Translational Neuroscience Program, Department of Psychiatry, University of Pennsylvania School of Medicine Philadelphia, PA, USA., Siegel SJ; Siegel Laboratory, Translational Neuroscience Program, Department of Psychiatry, University of Pennsylvania School of Medicine Philadelphia, PA, USA., Zukin RS; Zukin Laboratory, Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Yeshiva University Bronx, NY, USA., McDonald TV; McDonald Laboratory, Section of Molecular Cardiology, Departments of Medicine and Molecular Pharmacology, Albert Einstein College of Medicine, Yeshiva University Bronx, NY, USA., Bolduc FV; Bolduc Laboratory, Department of Pediatrics, Center for Neuroscience, University of Alberta Edmonton, AB, Canada., Jongens TA; Jongens Laboratory, Department of Genetics, University of Pennsylvania School of Medicine Philadelphia, PA, USA., McBride SM; McDonald Laboratory, Section of Molecular Cardiology, Departments of Medicine and Molecular Pharmacology, Albert Einstein College of Medicine, Yeshiva UniversityBronx, NY, USA; Jongens Laboratory, Department of Genetics, University of Pennsylvania School of MedicinePhiladelphia, PA, USA; Siegel Laboratory, Translational Neuroscience Program, Department of Psychiatry, University of Pennsylvania School of MedicinePhiladelphia, PA, USA.
Jazyk: angličtina
Zdroj: Frontiers in behavioral neuroscience [Front Behav Neurosci] 2016 Jun 30; Vol. 10, pp. 136. Date of Electronic Publication: 2016 Jun 30 (Print Publication: 2016).
DOI: 10.3389/fnbeh.2016.00136
Abstrakt: Fragile X is the most common monogenic disorder associated with intellectual disability (ID) and autism spectrum disorders (ASD). Additionally, many patients are afflicted with executive dysfunction, ADHD, seizure disorder and sleep disturbances. Fragile X is caused by loss of FMRP expression, which is encoded by the FMR1 gene. Both the fly and mouse models of fragile X are also based on having no functional protein expression of their respective FMR1 homologs. The fly model displays well defined cognitive impairments and structural brain defects and the mouse model, although having subtle behavioral defects, has robust electrophysiological phenotypes and provides a tool to do extensive biochemical analysis of select brain regions. Decreased cAMP signaling has been observed in samples from the fly and mouse models of fragile X as well as in samples derived from human patients. Indeed, we have previously demonstrated that strategies that increase cAMP signaling can rescue short term memory in the fly model and restore DHPG induced mGluR mediated long term depression (LTD) in the hippocampus to proper levels in the mouse model (McBride et al., 2005; Choi et al., 2011, 2015). Here, we demonstrate that the same three strategies used previously with the potential to be used clinically, lithium treatment, PDE-4 inhibitor treatment or mGluR antagonist treatment can rescue long term memory in the fly model and alter the cAMP signaling pathway in the hippocampus of the mouse model.
Databáze: MEDLINE