Vaynman S, Ying Z, Gomez-Pinilla F
Department of Physiological Science, UCLA, 621 Charles E. Young Drive, Los Angeles, CA 90095, USA.
Neuroscience. 2003;122(3):647-57. doi: 10.1016/j.neuroscience.2003.08.001.
This study was designed to identify molecular mechanisms by which exercise affects synaptic-plasticity in the hippocampus, a brain area whose function, learning and memory, depends on this capability. We have focused on the central role that brain-derived neurotrophic factor (BDNF) may play in mediating the effects of exercise on synaptic-plasticity. In fact, this impact of exercise is exemplified by our finding that BDNF regulates the mRNA levels of two end products important for neural function, i.e. cAMP-response-element binding (CREB) protein and synapsin I. CREB and synapsin I have the ability to modify neuronal function by regulating gene-transcription and affecting synaptic transmission, respectively. Furthermore, we show that BDNF is capable of concurrently increasing the mRNA levels of both itself and its tyrosine kinaseB (TrkB) receptor, suggesting that exercise may employ a feedback loop to augment the effects of BDNF on synaptic-plasticity. The use of a novel microbead injection method in our blocking experiments and Taqman reverse transcription polymerase reaction (RT-PCR) for RNA quantification, have enabled us to evaluate the contribution of different pathways to the exercise-induced increases in the mRNA levels of BDNF, TrkB, CREB, and synapsin I. We found that although BDNF mediates exercise-induced hippocampal plasticity, additional molecules, i.e. the N-methyl-D-aspartate receptor, calcium/calmodulin protein kinase II and the mitogen-activated protein kinase cascade, modulate its effects. Since these molecules have a well-described association to BDNF action, our results illustrate a basic mechanism through which exercise may promote synaptic-plasticity in the adult brain.
本研究旨在确定运动影响海马体突触可塑性的分子机制，海马体是一个脑区，其功能（学习和记忆）依赖于这种能力。我们聚焦于脑源性神经营养因子（BDNF）在介导运动对突触可塑性影响中可能发挥的核心作用。事实上，运动的这种影响体现在我们的发现中，即BDNF调节对神经功能重要的两种终产物的mRNA水平，即环磷酸腺苷反应元件结合（CREB）蛋白和突触素I。CREB和突触素I分别具有通过调节基因转录和影响突触传递来改变神经元功能的能力。此外，我们表明BDNF能够同时增加其自身及其酪氨酸激酶B（TrkB）受体的mRNA水平，这表明运动可能利用反馈回路来增强BDNF对突触可塑性的影响。在我们的阻断实验中使用新型微珠注射方法以及用于RNA定量的Taqman逆转录聚合酶反应（RT-PCR），使我们能够评估不同途径对运动诱导的BDNF、TrkB、CREB和突触素I的mRNA水平增加的贡献。我们发现，虽然BDNF介导运动诱导的海马体可塑性，但其他分子，即N-甲基-D-天冬氨酸受体、钙/钙调蛋白依赖性蛋白激酶II和丝裂原活化蛋白激酶级联反应，调节其作用。由于这些分子与BDNF的作用有充分描述的关联，我们的结果阐明了运动可能促进成人大脑突触可塑性的基本机制。
