Studies on the activity-dependent translational control in neurons

突触周围区活动依赖的局部翻译涉及突触范围内功能和形态的改变。然而，局部翻译激活的分子机制尚未被阐明。我们已经证明，脑源性神经营养因子（BDNF）以雷帕霉素敏感的方式上调神经元树突的局部蛋白质合成和翻译激活。同时，BDNF激活哺乳动物树突中雷帕霉素靶蛋白（mTOR）信号通路。BDNF还通过mTOR途径增强了延伸过程。雷帕霉素抑制mTOR活性和siRNA敲低mTOR可完全抑制BDNF的作用。目前的研究结果表明，在多个过程中，mtor依赖的翻译激活对于神经元树突局部蛋白质合成的上调至关重要。我们进一步证明mtor依赖的翻译激活发生在可塑性事件中，如中枢神经系统的LTP和空间记忆范式。由于雷帕霉素取消了这些作用，mtor依赖的翻译激活对于某些类型的神经可塑性是必不可少的。

Activity-dependent local translation at the perisynaptic area is implicated in synapse-wide alterations of function and morphology. The molecular mechanisms of local translation activation, however, have yet to be illuminated. We have shown that local protein synthesis and translational activation in neuronal dendrites were up-regulated by brain-derived neurotrophic factor (BDNF) in a rapamycin-sensitive manner. In parallel, BDNF activates of mammalian target of rapamycin (mTOR) signaling pathways in dendrites. BDNF also enhances elongation process through the mTOR pathway. Inhibition of mTOR activity by rapamycin and knockdown of mTOR by siRNA completely suppresses the action of BDNF.The present results indicate that mTOR-dependent translation activation at multiple processes is essential for the up-regulation of local protein synthesis in neuronal dendrites. We further showed the evidences that mTOR-dependent translational activation occurred during plastic event, such as LTP and spatial memory paradigms in the CNS. As rapamycin canceled these effects, mTOR-dependent translational activation is essential for the certain types of neural plasticity.