Reduced activity-dependent protein levels in a mouse model of the fragile X premutation

RE von Leden, LC Curley, GD Greenberg, MR Hunsaker, Rob Willemsen, RF Berman

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Environmental enrichment results in increased levels of Fmrp in brain and increased dendritic complexity. The present experiment evaluated activity-dependent increases in Fmrp levels in the motor cortex in response to training on a skilled forelimb reaching task in the CGG RI mouse model of the fragile X premutation. Fmrp, Arc, and c-Fos protein levels were quantified by Western blot in the contralateral motor cortex of mice following training to reach for sucrose pellets with a non-preferred paw and compared to levels in the ipsilateral motor cortex. After training, all mice showed increases in Fmrp, Arc, and c-Fos protein levels in the contralateral compared to the ipsilateral hemisphere; however, the increase in CGG RI mice was less than wildtype mice. Increases in Fmrp and Arc proteins scaled with learning, whereas this relationship was not observed with the c-Fos levels. These data suggest the possibility that reduced levels of activity-dependent proteins associated with synaptic plasticity such as Fmrp and Arc may contribute to the neurocognitive phenotype reported in the CGG KI mice and the fragile X premutation. (C) 2014 Elsevier Inc. All rights reserved.
Original languageUndefined/Unknown
Pages (from-to)160-168
Number of pages9
JournalNeurobiology of Learning and Memory
Publication statusPublished - 2014

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  • EMC MGC-02-96-01

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