Section on Neural Development and Plasticity, National Institute of Child Health and Human Development, Bethesda, Maryland, USA.
Nat Neurosci. 2010 Mar;13(3):302-9. doi: 10.1038/nn.2505. Epub 2010 Feb 21.
Extracellular factors may act on cells in two distinct modes: an acute increase in concentration as a result of regulated secretion, or a gradual increase in concentration when secreted constitutively or from a distant source. We found that cellular responses to brain-derived neurotrophic factor (BDNF) differed markedly depending on how BDNF was delivered. In cultured rat hippocampal neurons, acute and gradual increases in BDNF elicited transient and sustained activation of TrkB receptor and its downstream signaling, respectively, leading to differential expression of Homer1 and Arc. Transient TrkB activation promoted neurite elongation and spine head enlargement, whereas sustained TrkB activation facilitated neurite branch and spine neck elongation. In hippocampal slices, fast and slow increases in BDNF enhanced basal synaptic transmission and LTP, respectively. Thus, the kinetics of TrkB activation is critical for cell signaling and functions. This temporal dimension in cellular signaling may also have implications for the therapeutic drug design.
一种是由于调节性分泌导致浓度的急性增加，另一种是当以组成型或从远处来源分泌时浓度的逐渐增加。我们发现，细胞对脑源性神经营养因子 (BDNF) 的反应取决于 BDNF 的传递方式。在培养的大鼠海马神经元中，BDNF 的急性和逐渐增加分别引起 TrkB 受体及其下游信号的短暂和持续激活，导致 Homer1 和 Arc 的差异表达。短暂的 TrkB 激活促进神经突伸长和棘突头部增大，而持续的 TrkB 激活促进神经突分支和棘突颈部伸长。在海马切片中，BDNF 的快速和缓慢增加分别增强了基础突触传递和 LTP。因此，TrkB 激活的动力学对细胞信号转导和功能至关重要。这种细胞信号的时间维度也可能对治疗药物设计具有重要意义。
