Reduced activity-dependent protein levels in a mouse model of the fragile X premutation.
Reduced activity-dependent protein levels in a mouse model of the fragile X premutation.
复制标题
脆性 X 前突变小鼠模型中活性依赖性蛋白水平降低。
DOI：
10.1016/j.nlm.2014.01.011
复制
发表时间：
2014
影响因子：
2.7
通讯作者：
Berman,RobertF
中科院分区：
文献类型：
--
作者：
vonLeden,RamonaE;Curley,LindseyC;Greenberg,GianD;Hunsaker,MichaelR;Willemsen,Rob;Berman,RobertF
环境富集导致脑内Fmrp水平升高和树突复杂性增加。本实验在脆性X基因突变的CGG - KI小鼠模型中评估了在熟练的前肢到达任务训练后，运动皮层中Fmrp水平的活动依赖性增加。在训练用非首选的爪子去拿蔗糖颗粒后，用Western blot方法定量了小鼠对侧运动皮层中的Fmrp、Arc和c-Fos蛋白水平，并与同侧运动皮层中的水平进行了比较。训练后，与同侧半球相比，所有小鼠的对侧半球Fmrp、Arc和c-Fos蛋白水平均有所增加；然而，CGG - KI小鼠的增加幅度小于野生型小鼠。Fmrp和Arc蛋白的增加与学习成比例，而这种关系与c-Fos水平没有观察到。这些数据表明，与突触可塑性相关的活动依赖蛋白（如Fmrp和Arc）水平的降低可能有助于CGG KI小鼠和脆性X前兆突变中报道的神经认知表型。
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.