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Article

Carbamazepine Restores Neuronal Signaling, Protein Synthesis, and Cognitive Function in a Mouse Model of Fragile X Syndrome

by 1, 1,†, 2 and 1,3,*
1
Department of Physiology, Michigan State University, East Lansing, MI 48824, USA
2
Department of Pharmacology and Chemical Biology, Emory University School of Medicine, Atlanta, GA 30322, USA
3
Neuroscience Program, Michigan State University, East Lansing, MI 48824, USA
*
Author to whom correspondence should be addressed.
Current address: College of Life Science and Agriculture, Zhoukou Normal College, Zhoukou 466000, China.
Int. J. Mol. Sci. 2020, 21(23), 9327; https://doi.org/10.3390/ijms21239327
Received: 24 October 2020 / Revised: 19 November 2020 / Accepted: 3 December 2020 / Published: 7 December 2020
Fragile X syndrome (FXS) is a leading genetic disorder of intellectual disability caused by the loss of the functional fragile X mental retardation protein (FMRP). To date, there is no efficacious mechanism-based medication for FXS. With regard to potential disease mechanisms in FXS, it is widely accepted that the lack of FMRP causes elevated protein synthesis and deregulation of neuronal signaling. Abnormal enhancement of the ERK½ (extracellular signal-regulated kinase ½) and PI3K-Akt (Phosphoinositide 3 kinase-protein kinase B) signaling pathways has been identified in both FXS patients and FXS mouse models. In this study, we show that carbamazepine, which is an FDA-approved drug and has been mainly used to treat seizure and neuropathic pain, corrects cognitive deficits including passive avoidance and object location memory in FXS mice. Carbamazepine also rescues hyper locomotion and social deficits. At the cellular level, carbamazepine dampens the elevated level of ERK½ and Akt signaling as well as protein synthesis in FXS mouse neurons. Together, these results advocate repurposing carbamazepine for FXS treatment. View Full-Text
Keywords: fragile X syndrome; therapeutics; mouse model; carbamazepine; type 1 adenylyl cyclase; phosphodiesterase; cAMP; ERK½; PI3 kinase; protein translation; intellectual disability; learning and memory; drug repurposing fragile X syndrome; therapeutics; mouse model; carbamazepine; type 1 adenylyl cyclase; phosphodiesterase; cAMP; ERK½; PI3 kinase; protein translation; intellectual disability; learning and memory; drug repurposing
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MDPI and ACS Style

Ding, Q.; Zhang, F.; Feng, Y.; Wang, H. Carbamazepine Restores Neuronal Signaling, Protein Synthesis, and Cognitive Function in a Mouse Model of Fragile X Syndrome. Int. J. Mol. Sci. 2020, 21, 9327. https://doi.org/10.3390/ijms21239327

AMA Style

Ding Q, Zhang F, Feng Y, Wang H. Carbamazepine Restores Neuronal Signaling, Protein Synthesis, and Cognitive Function in a Mouse Model of Fragile X Syndrome. International Journal of Molecular Sciences. 2020; 21(23):9327. https://doi.org/10.3390/ijms21239327

Chicago/Turabian Style

Ding, Qi, Fan Zhang, Yue Feng, and Hongbing Wang. 2020. "Carbamazepine Restores Neuronal Signaling, Protein Synthesis, and Cognitive Function in a Mouse Model of Fragile X Syndrome" International Journal of Molecular Sciences 21, no. 23: 9327. https://doi.org/10.3390/ijms21239327

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