Department of Chemistry, Stanford University, Stanford, CA, USA.
Integr Biol (Camb). 2012 Aug;4(8):953-60. doi: 10.1039/c2ib20062g. Epub 2012 Jul 6.
Brain derived neurotrophic factor (BDNF) plays a key role in the growth, development and maintenance of the central and peripheral nervous systems. Exogenous BDNF activates its membrane receptors at the axon terminal, and subsequently sends regulation signals to the cell body. To understand how a BDNF signal propagates in neurons, it is important to follow the trafficking of BDNF after it is internalized at the axon terminal. Here we labeled BDNF with bright, photostable quantum dots (QD-BDNF) and followed the axonal transport of QD-BDNF in real time in hippocampal neurons. We showed that QD-BDNF was able to bind BDNF receptors and activate downstream signaling pathways. When QD-BDNF was applied to the distal axons of hippocampal neurons, it was observed to be actively transported toward the cell body at an average speed of 1.11 ± 0.05 μm s(-1). A closer examination revealed that QD-BDNF was transported by both discrete endosomes and multivesicular body-like structures. Our results showed that QD-BDNF could be used to track the movement of exogenous BDNF in neurons over long distances and to study the signaling organelles that contain BDNF.
脑源性神经营养因子（BDNF）在中枢和周围神经系统的生长、发育和维持中起着关键作用。外源性 BDNF 在轴突末梢激活其膜受体，然后向细胞体发送调节信号。为了了解 BDNF 信号如何在神经元中传播，重要的是要跟踪 BDNF 在轴突末梢内化后的运输情况。在这里，我们用明亮、光稳定的量子点（QD-BDNF）标记 BDNF，并实时跟踪海马神经元中 QD-BDNF 的轴突运输。我们表明，QD-BDNF 能够结合 BDNF 受体并激活下游信号通路。当 QD-BDNF 被施加到海马神经元的远端轴突时，观察到它以 1.11±0.05μm s(-1)的平均速度向细胞体主动运输。更仔细的检查表明，QD-BDNF 是由离散的内体和多泡体样结构共同运输的。我们的结果表明，QD-BDNF 可用于追踪神经元中外源性 BDNF 的远距离运动，并研究含有 BDNF 的信号细胞器。
