Reduced activity-dependent protein levels in a mouse model of the fragile X premutation.
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 KI 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 KI 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.
Department of Neurological Surgery, School of Medicine, University of California, Davis, Davis, CA, USA.
Ramona E
RE
von Leden
Department of Neurological Surgery, School of Medicine, University of California, Davis, Davis, CA, USA.
Lindsey C
LC
Curley
Department of Psychology, University of California, Davis, Davis, CA, USA.
Gian D
GD
Greenberg
Department of Neurological Surgery, School of Medicine, University of California, Davis, Davis, CA, USA. Electronic address: mrhunsaker@icloud.com.
Michael R
MR
Hunsaker
CBG-Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands; NeuroTherapeutic Research Institute, University of California, Davis, Davis, CA, USA.
Rob
R
Willemsen
Department of Neurological Surgery, School of Medicine, University of California, Davis, Davis, CA, USA; NeuroTherapeutic Research Institute, University of California, Davis, Davis, CA, USA.
Robert F
RF
Berman
D000818:Animals; D004195:Disease Models, Animal; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics / Q000378:metabolism*; D005600:Fragile X Syndrome / Q000235:genetics / Q000378:metabolism*; D055879:Gene Knock-In Techniques; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000502:physiology*; D009044:Motor Cortex / Q000378:metabolism*; D009154:Mutation
D051860:Fragile X Messenger Ribonucleoprotein 1; C497684:Fmr1 protein, mouse
Arc; CGG KI mouse; Endophenotype; Fmrp; Fragile X premutation; Western blot; c-Fos