Neurotrophins and their role in the cochlea
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Background: Neurotrophins like brain derived neurotrophic factor (BDNF) and nerve growth factor (NGF) are neuroprotective and prevent cell death during ischemic conditions. BDNF and NGF expression have been shown to increase after hypoxia in animal studies. However, the effect of hypoxia on systemic release of BDNF and NGF in vivo has not been thoroughly studied. We investigated the impact of acute hypoxia on plasma concentrations of BDNF and NGF in healthy men.
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在哺乳动物的大脑，四 neurotrophins 被识别了：神经生长因素(NGF ) ，导出大脑的神经营养的因素(BDNF ) ， neurotrophin-3 (NT-3 ) 和 neurotrophin-4/5 (NT-4/5 ) 。NGF 在中央、外部的神经系统的开发和函数施加一个重要角色。然而，有免疫力的房间的几种类型例如桅杆房间，淋巴细胞， basophils 和嗜曙红血球，生产，存储并且释放 NGF，这最近被记录了。积累现出症状之前的潜、临床的数据显示 NGF 和另外的 neurotrophins 的机能障碍可以贡献损害有免疫力的回答， NGF 的集中经常与疾病严厉相关。因此，这研究的目的是阐明贡献的 cytokineneurotrophins 相互作用的潜在的发信号机制增加了 NGF 层次。我们抄写 factorNF-B 玩的数据表演在调整 B-cell-derived NGF 的一个枢轴的角色表示。
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The development and survival of sympathetic neurons is critically dependent on the related neurotrophic factors nerve growth factor (NGF) and neurotrophin-3 (NT3), the actions of which must be executed appropriately despite spatial and temporal overlaps in their activities. The tyrosine receptor kinases, trkA and trkC, are the cognate receptors for NGF and NT3, respectively. The p75 neurotrophin receptor has been implicated in neurotrophin binding and signaling for both NGF and NT3. In this study, the authors used mice that overexpressed NGF (NGF-OE) or NT3 (NT3-OE) in skin and mice that lacked p75 (p75−/−) to understand the dynamics of sympathetic neuron response to each neurotrophin and to address the role of p75. NGF and NT3 were measured in sympathetic ganglia and skin (a major target of sympathetic neurons) by using the enzyme-linked immunosorbent assay (ELISA) technique. A three- to four-fold increase in skin NT3 was seen in both NT3-OE and p75−/− mice. Moreover, both mouse lines exhibited a three-fold increase in ganglionic NT3. However, the increase in ganglionic NT3 was accompanied by a decrease in ganglionic NGF in p75−/− mice but not in NT3-OE mice. This indicated that p75 plays an important role in determining the level of NGF within sympathetic neurons. In NGF-OE mice, the overexpression of NGF was correlated with increased ganglionic NGF and increased ganglionic expression of p75 mRNA. In addition, in NGF-OE mice, ganglionic trkC expression was decreased, as was the amount of NT3 present within sympathetic ganglia. These results indicate that the level of p75 is integral in determining the level of sympathetic NGF and that NGF competes with NT3 by increasing the expression of p75 and decreasing the expression of trkC. J. Comp. Neurol. 424:99–110, 2000. © 2000 Wiley-Liss, Inc.
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We used compartmented cultures to study the regulation of adult sensory neurite growth by neurotrophins. We examined the effects of the neurotrophins nerve growth factor (NGF), neurotrophin-3 (NT3), and BDNF on distal neurite elongation from adult rat dorsal root ganglion (DRG) neurons. Neurons were plated in the center compartments of three-chambered dishes in the absence of neurotrophin, and neurite extension into the distal (side) compartments containing NGF, BDNF, or NT3 was quantitated. Initial proximal neurite growth did not require any of the neurotrophins, while subsequent elongation into distal compartments required NGF. After neurites had extended into NGF-containing distal compartments, removal of NGF by treatment with anti-NGF resulted in the cessation of growth with minimal neurite retraction. In contrast to the effects of NGF, no distal neurite elongation was observed into compartments with BDNF or NT3. To examine possible additive influences, neurite extension into compartments containing BDNF plus NGF or NT3 plus NGF was quantitated. There was no increased neurite extension into NGF plus NT3 compartments, while the combination of BDNF plus NGF resulted in an inhibition of neurite extension compared with NGF alone. We then investigated whether the regrowth of neurites that had originally grown into NGF subsequent to in vitro axotomy still required NGF. The results demonstrated that unlike adult sensory nerve regeneration in vivo, the in vitro regrowth did require NGF, and neither BDNF nor NT3 was able to substitute for NGF. Since the initial growth from neurons after dissociation (which is also a regenerative response) did not require NGF, it would appear that neuritic growth and regrowth of adult DRG neurons in vitro includes both NGF-independent and NGF-dependent components. The compartmented culture system provides a unique model to further study aspects of this differential regulation of neurite growth. © 1997 John Wiley & Sons, Inc. J Neurobiol 33: 395–410, 1997
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