AUTHOR=Choi Catherine H. , Schoenfeld Brian P. , Bell Aaron J. , Hinchey Joseph , Rosenfelt Cory , Gertner Michael J. , Campbell Sean R. , Emerson Danielle , Hinchey Paul , Kollaros Maria , Ferrick Neal J. , Chambers Daniel B. , Langer Steven , Sust Steven , Malik Aatika , Terlizzi Allison M. , Liebelt David A. , Ferreiro David , Sharma Ali , Koenigsberg Eric , Choi Richard J. , Louneva Natalia , Arnold Steven E. , Featherstone Robert E. , Siegel Steven J. , Zukin R. Suzanne , McDonald Thomas V. , Bolduc Francois V. , Jongens Thomas A. , McBride Sean M. J. TITLE=Multiple Drug Treatments That Increase cAMP Signaling Restore Long-Term Memory and Aberrant Signaling in Fragile X Syndrome Models JOURNAL=Frontiers in Behavioral Neuroscience VOLUME=10 YEAR=2016 URL=https://www.frontiersin.org/journals/behavioral-neuroscience/articles/10.3389/fnbeh.2016.00136 DOI=10.3389/fnbeh.2016.00136 ISSN=1662-5153 ABSTRACT=

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.