Effects of the neurotrophins nerve growth factor, neurotrophin-3, and brain-derived neurotrophic factor (BDNF) on neurite growth from adult sensory neurons in compartmented cultures

Effects of the neurotrophins nerve growth factor, neurotrophin-3, and brain-derived neurotrophic factor (BDNF) on neurite growth from adult sensory neurons in compartmented cultures
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DOI:
10.1002/(sici)1097-4695(199710)33:4
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发表时间:
1997-10-01
期刊:
JOURNAL OF NEUROBIOLOGY
影响因子:
--
通讯作者:
Mearow, K
Mearow, K
中科院分区:
其他
文献类型:
--
作者:
Kimpinski, K;Campenot, RB;Mearow, K

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我们采用区隔培养法研究神经营养因子对成人感觉神经突生长的调节作用。我们研究了神经营养因子神经生长因子(NGF)、神经营养因子-3 (NT3)和BDNF对成年大鼠背根神经节(DRG)神经元远端神经突伸长的影响。在没有神经营养因子的情况下,在三室培养皿的中心室中培育神经元,并量化神经突向含有NGF、BDNF或NT3的远端(侧)室的延伸。最初的近端神经突起生长不需要任何神经营养物质,而随后延伸到远端神经室则需要神经生长因子。当神经突延伸到含有NGF的远端腔室后,用抗NGF治疗去除NGF导致神经突收缩最小的生长停止。与NGF的作用相反,BDNF或NT3没有观察到远端神经突延伸到隔室。为了检查可能的附加影响,神经突延伸到含有BDNF + NGF或NT3 + NGF的隔室被量化。神经突向NGF + NT3间室的延伸没有增加,而BDNF + NGF联合使用与单独使用NGF相比,神经突的延伸受到抑制。然后,我们研究了体外轴突切开术后原本生长为神经生长因子的神经突的再生是否仍然需要神经生长因子。结果表明,与体内成人感觉神经再生不同,体外再生确实需要NGF,而且BDNF和NT3都不能替代NGF。由于分离后神经元的初始生长(这也是一种再生反应)不需要NGF,因此成人DRG神经元的体外神经炎生长和再生似乎包括NGF独立和NGF依赖的成分。区隔培养系统为进一步研究神经突生长的差异调节方面提供了一个独特的模型。(C) 1997 John Wiley & Sons公司
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 prated 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. (C) 1997 John Wiley & Sons, Inc.