CNC-Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal; Department of Life Sciences, University of Coimbra, 3004-517 Coimbra, Portugal.
Neuropharmacology. 2014 Jan;76 Pt C:639-56. doi: 10.1016/j.neuropharm.2013.04.005. Epub 2013 Apr 16.
Brain-derived neurotrophic factor (BDNF) is an important regulator of synaptic transmission and long-term potentiation (LTP) in the hippocampus and in other brain regions, playing a role in the formation of certain forms of memory. The effects of BDNF in LTP are mediated by TrkB (tropomyosin-related kinase B) receptors, which are known to be coupled to the activation of the Ras/ERK, phosphatidylinositol 3-kinase/Akt and phospholipase C-γ (PLC-γ) pathways. The role of BDNF in LTP is best studied in the hippocampus, where the neurotrophin acts at pre- and post-synaptic levels. Recent studies have shown that BDNF regulates the transport of mRNAs along dendrites and their translation at the synapse, by modulating the initiation and elongation phases of protein synthesis, and by acting on specific miRNAs. Furthermore, the effect of BDNF on transcription regulation may further contribute to long-term changes in the synaptic proteome. In this review we discuss the recent progress in understanding the mechanisms contributing to the short- and long-term regulation of the synaptic proteome by BDNF, and the role in synaptic plasticity, which is likely to influence learning and memory formation. This article is part of the Special Issue entitled 'BDNF Regulation of Synaptic Structure, Function, and Plasticity'.
脑源性神经营养因子(BDNF)是海马体和其他脑区中突触传递和长时程增强(LTP)的重要调节因子,在某些形式的记忆形成中发挥作用。BDNF 在 LTP 中的作用是通过 TrkB(原肌球蛋白相关激酶 B)受体介导的,已知 TrkB 受体与 Ras/ERK、磷脂酰肌醇 3-激酶/Akt 和磷脂酶 C-γ(PLC-γ)途径的激活偶联。BDNF 在 LTP 中的作用在海马体中研究得最好,神经生长因子在突触前和突触后水平发挥作用。最近的研究表明,BDNF 通过调节蛋白质合成的起始和延伸阶段,以及作用于特定的 miRNA,调节 mRNA 沿树突的运输及其在突触处的翻译。此外,BDNF 对转录调控的影响可能进一步有助于突触蛋白组的长期变化。在这篇综述中,我们讨论了理解 BDNF 对突触蛋白组的短期和长期调节的机制的最新进展,以及 BDNF 在突触可塑性中的作用,这可能影响学习和记忆的形成。本文是题为“BDNF 调节突触结构、功能和可塑性”的特刊的一部分。