Soulé J, Messaoudi E, Bramham C R
Department of Biomedicine and Bergen Mental Health Research Center, University of Bergen, Jonas Lies vei 91, N-5009 Bergen, Norway.
Biochem Soc Trans. 2006 Aug;34(Pt 4):600-4. doi: 10.1042/BST0340600.
Interest in BDNF (brain-derived neurotrophic factor) as an activity-dependent modulator of neuronal structure and function in the adult brain has intensified in recent years. Localization of BDNF and its receptor tyrosine kinase TrkB (tropomyosin receptor kinase B) to glutamate synapses makes this system attractive as a dynamic, activity-dependent regulator of excitatory transmission and synaptic plasticity in the adult brain. Development of stable LTP (long-term potentiation) in response to high-frequency stimulation requires new gene expression and protein synthesis, a process referred to as synaptic consolidation. Several lines of evidence have implicated endogenous BDNF-TrkB signalling in synaptic consolidation. This mini-review emphasizes new insights into the molecular mechanisms underlying this process. The immediate early gene Arc (activity-regulated cytoskeleton-associated protein) is strongly induced and transported to dendritic processes after LTP induction in the dentate gyrus in live rats. Recent work suggests that sustained synthesis of Arc during a surprisingly protracted time-window is required for hyperphosphorylation of actin-depolymerizing factor/cofilin and local expansion of the actin cytoskeleton in vivo. Moreover, this process of Arc-dependent synaptic consolidation is activated in response to brief infusion of BDNF. Microarray expression profiling has also revealed a panel of BDNF-regulated genes that may co-operate with Arc during LTP maintenance. In addition to regulating gene expression, BDNF signalling modulates the fine localization and biochemical activation of the translation machinery. By modulating the spatial and temporal translation of newly induced (Arc) and constitutively expressed mRNA in neuronal dendrites, BDNF may effectively control the window of synaptic consolidation. These findings have implications for mechanisms of memory storage and mood control.
近年来，脑源性神经营养因子（BDNF）作为成年大脑中神经元结构和功能的一种活动依赖性调节剂，受到了越来越多的关注。BDNF及其受体酪氨酸激酶TrkB（原肌球蛋白受体激酶B）定位于谷氨酸突触，这使得该系统作为成年大脑中兴奋性传递和突触可塑性的动态、活动依赖性调节剂颇具吸引力。响应高频刺激而产生稳定的长时程增强（LTP）需要新的基因表达和蛋白质合成，这一过程被称为突触巩固。多条证据表明内源性BDNF-TrkB信号传导参与突触巩固。这篇小型综述着重介绍了对这一过程潜在分子机制的新见解。在活鼠齿状回中诱导LTP后，立即早期基因Arc（活动调节细胞骨架相关蛋白）被强烈诱导并转运至树突过程。最近的研究表明，在体内肌动蛋白解聚因子/丝切蛋白的过度磷酸化和肌动蛋白细胞骨架的局部扩张需要在一个出人意料的长时间窗口内持续合成Arc。此外，响应短暂注入BDNF可激活这种依赖Arc的突触巩固过程。微阵列表达谱分析还揭示了一组BDNF调节的基因，它们可能在LTP维持过程中与Arc协同作用。除了调节基因表达外，BDNF信号传导还调节翻译机制的精细定位和生化激活。通过调节神经元树突中新诱导（Arc）和组成型表达mRNA的空间和时间翻译，BDNF可能有效地控制突触巩固的窗口。这些发现对记忆存储和情绪控制机制具有启示意义。
