Anterograde transport and secretion of brain-derived neurotrophic factor along sensory axons promote schwann cell myelination
Anterograde transport and secretion of brain-derived neurotrophic factor along sensory axons promote schwann cell myelination
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DOI：
10.1523/jneurosci.0563-07.2007
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发表时间：
2007-07-11
影响因子：
5.3
通讯作者：
Chan, Jonah R.
中科院分区：
文献类型：
--
作者：
Ng, Benjamin K.;Chen, Lian;Chan, Jonah R.
神经营养蛋白脑源性神经营养因子 (BDNF) 通过 p75 神经营养蛋白受体 (NTR) 抑制雪旺细胞 (SC) 迁移并促进髓鞘形成。尽管有这些最新发现，BDNF 的表达、定位和作用机制仍有待确定。在这里，我们证明背根神经节（DRG）的感觉神经元是出生后发育过程中 BDNF 的主要来源。 BDNF 的表达在髓鞘形成之前最初升高，并在髓鞘形成开始后急剧下降。 BDNF 表达部分受到转录调控和 SC 上截短 TrkB 受体表达增加的控制。为了研究 BDNF 转运和释放的可能机制，使用了多室 Campenot 室。 DRG 神经元沿轴突表面以顺行方式运输和分泌内源性 BDNF。为了通过 SC 增强髓鞘形成，DRG 神经元被腺病毒转导以过度表达 BDNF。与对照共培养物相比，BDNF 沿着轴突运输和分泌，髓鞘形成增强。总之，围绕 DRG 神经元中 BDNF 的表达、定位和作用机制的事件可能暗示着有效促进髓鞘再生的潜在治疗意义。
The neurotrophin brain-derived neurotrophic factor ( BDNF) inhibits Schwann cell (SC) migration and promotes myelination via the p75 neurotrophin receptor (NTR). Despite these recent findings, the expression, localization, and mechanism of BDNF action has yet to be determined. Here we demonstrate that the sensory neurons of the dorsal root ganglion (DRG) are a major source of BDNF during postnatal development. The expression of BDNF is initially elevated before myelination and decreases dramatically after the onset of myelination. BDNF expression is controlled in part by transcriptional regulation and the increased expression of the truncated TrkB receptor on SCs. To investigate the possible mechanism of BDNF transport and release, multicompartment Campenot chambers were used. DRG neurons transported and secreted endogenous BDNF along the surface of axons in anterograde fashion. In an attempt to enhance myelination by SCs, DRG neurons were transduced with an adenovirus to overexpress BDNF. BDNF was transported and secreted along the axons and enhanced myelination when compared with control cocultures. Together, the events surrounding the expression, localization, and mechanism of BDNF action in DRG neurons may hint at potential therapeutic implications to efficiently promote remyelination.