摘要
Willed-movement training has been demonstrated to be a promising approach to increase motor per- formance and neural plasticity in ischemic rats. However, little is known regarding the molecular signals that are in- volved in neural plasticity following willed-movement training. To investigate the potential signals related to neural plasticity following willed-movement training, littermate rats were randomly assigned into three groups: middle cerebral artery occlusion, environmental modification, and willed-movement training. The infarct volume was measured 18 d after occlusion of the right middle cerebral artery. Reverse transcription-polymerase chain reaction (PCR) and im- munofluorescence staining were used to detect the changes in the signal transducer and activator of transcription 3 (STAT3) mRNA and protein, respectively. A chromatin immunoprecipitation was used to investigate whether STAT3 bound to plasticity-related genes, such as brain-derived neurotrophic factor (BDNF), synaptophysin, and protein in- teracting with C kinase 1 (PICK1). In this study, we demonstrated that STAT3 mRNA and protein were markedly increased following 15-d willed-movement training in the ischemic hemispheres of the treated rats. STAT3 bound to BDNF, PICK1, and synaptophysin promoters in the neocortical cells of rats. These data suggest that the increased STAT3 levels after willed-movement training might play critical roles in the neural plasticity by directly regulating plasticity-related genes.
目的:探讨意向性运动疗法干预后与神经可塑性相关的信号通路。创新点:首次发现意向性运动疗法干预后信号传导与转录激活因子3(STAT3)表达增高,以及STAT3直接调控神经可塑性相关基因。方法:将大脑中动脉梗死(MCAO)模型大鼠随机分为MCAO组、环境改变组和意向性运动疗法组。18天后测量三组大鼠的脑梗死面积。应用逆转录聚合酶链反应(RT-PCR)和荧光免疫染色法分别检测STAT3的基因和蛋白的表达;应用染色质免疫共沉淀检测STAT3是否绑定脑源性神经营养因子(BDNF)、突触素以及蛋白激酶Cα相互作用蛋白1(PICK1)。结论:研究结果显示:意向性运动疗法干预15天后,STAT3的基因与蛋白均增高;STAT3绑定皮层神经元BDNF、PICK1和突触素的启动子区;意向性运动干预后STAT3的升高可能与神经可塑性相关。
基金
Project supported by the National Natural Science Foundation of China(Nos.30973167,81472160,and 81173595)
the China Postdoctoral Science Foundation(Nos.2011M501301 and 2012T50711)
the China-Japan Friendship Hospital Youth Science and Technology Excellence Project(No.2014-QNYC-A-04)