Multiple drug treatments thatincrease cAMP signaling restorelong-term memory and aberrantsignaling in fragile X syndromemodels

Catherine H. Choi, Brian P. Schoenfeld, Aaron J. Bell, Joseph Hinchey, Cory Rosenfelt, Michael J. Gertner, Sean R. Campbell, Danielle Emerson, Paul Hinchey, Maria Kollaros, Neal J. Ferrick, Daniel B. Chambers, Steven Langer, Steven Sust, Aatika Malik, Allison M. Terlizzi, David A. Liebelt, David Ferreiro, Ali Sharma, Eric KoenigsbergRichard J. Choi, Natalia Louneva, Steven E. Arnold, Robert E. Featherstone, Steven J. Siegel, R. Suzanne Zukin, Thomas V. McDonald, Francois V. Bolduc, Thomas A. Jongens, Sean M J McBride

Research output: Contribution to journalArticle

16 Citations (Scopus)

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.

Original languageEnglish (US)
Article number136
JournalFrontiers in Behavioral Neuroscience
Volume10
Issue numberJun
DOIs
StatePublished - Jun 30 2016

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Diptera
Pharmaceutical Preparations
Hippocampus
Phosphodiesterase 4 Inhibitors
Therapeutics
Long-Term Memory
Brain
Short-Term Memory
Lithium
Intellectual Disability
Epilepsy
Sleep
Depression
Phenotype
Genes
Proteins

Keywords

  • Fragile X
  • Group II mGluR
  • GSK-3β
  • Lithium
  • MTOR
  • PDE-4
  • Tau

ASJC Scopus subject areas

  • Behavioral Neuroscience
  • Cognitive Neuroscience
  • Neuropsychology and Physiological Psychology

Cite this

Choi, C. H., Schoenfeld, B. P., Bell, A. J., Hinchey, J., Rosenfelt, C., Gertner, M. J., ... McBride, S. M. J. (2016). Multiple drug treatments thatincrease cAMP signaling restorelong-term memory and aberrantsignaling in fragile X syndromemodels. Frontiers in Behavioral Neuroscience, 10(Jun), [136]. https://doi.org/10.3389/fnbeh.2016.00136

Multiple drug treatments thatincrease cAMP signaling restorelong-term memory and aberrantsignaling in fragile X syndromemodels. / 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.

In: Frontiers in Behavioral Neuroscience, Vol. 10, No. Jun, 136, 30.06.2016.

Research output: Contribution to journalArticle

Choi, CH, Schoenfeld, BP, Bell, AJ, Hinchey, J, Rosenfelt, C, Gertner, MJ, Campbell, SR, Emerson, D, Hinchey, P, Kollaros, M, Ferrick, NJ, Chambers, DB, Langer, S, Sust, S, Malik, A, Terlizzi, AM, Liebelt, DA, Ferreiro, D, Sharma, A, Koenigsberg, E, Choi, RJ, Louneva, N, Arnold, SE, Featherstone, RE, Siegel, SJ, Zukin, RS, McDonald, TV, Bolduc, FV, Jongens, TA & McBride, SMJ 2016, 'Multiple drug treatments thatincrease cAMP signaling restorelong-term memory and aberrantsignaling in fragile X syndromemodels', Frontiers in Behavioral Neuroscience, vol. 10, no. Jun, 136. https://doi.org/10.3389/fnbeh.2016.00136
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. / Multiple drug treatments thatincrease cAMP signaling restorelong-term memory and aberrantsignaling in fragile X syndromemodels. In: Frontiers in Behavioral Neuroscience. 2016 ; Vol. 10, No. Jun.
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