Characterization of bone morphogenetic protein family members as neurotrophic factors for cultured sensory neurons
Characterization of bone morphogenetic protein family members as neurotrophic factors for cultured sensory neurons
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DOI：
10.1016/s0306-4522(98)00735-0
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发表时间：
1999-01-01
期刊：
影响因子：
3.3
通讯作者：
Krieglstein, K
中科院分区：
文献类型：
--
作者：
Farkas, LM;Jászai, J;Krieglstein, K
骨形态发生蛋白参与了脊椎动物发育过程中的几个诱导过程，包括神经系统的形成。最近，这些蛋白质也成为调节中脑多巴胺能和交感神经元存活的候选者。有趣的是，我们已经发现，几个骨形态发生蛋白可以检测到在发育胚胎第14天大鼠背根神经节通过逆转录-聚合酶链反应和免疫细胞化学。为了进一步阐明它们在个体发育神经元死亡期间的潜在作用，用不同的骨形态发生蛋白处理来自发育中的鸡和大鼠胚胎的背根感觉神经元的无血清培养物，同时加入或不加入其他“已建立的”神经营养因子。我们的研究结果表明，骨形态发生蛋白发挥自己的生存促进作用，他们可以积极调节神经营养素对感觉神经元的影响。特别是，生长分化因子-5、骨形态发生蛋白-2、-4、-7和-12显著增强了神经营养因子-3和神经生长因子对培养的背根神经节神经元的促存活作用，这些结果很好地符合目前神经营养因子可能协同作用以确保神经元存活的概念。此外，这些数据表明在感觉神经元发育过程中骨形态发生蛋白和神经营养因子的潜在指导性相互作用。最后，骨形态发生蛋白家族成员的神经营养能力可能与周围神经病变的治疗有潜在的相关性。(C)1999年IBRO。出版社：Elsevier Science Ltd
The bone morphogenetic proteins have been implicated in several inductive processes throughout vertebrate development including nervous system patterning. Recently, these proteins have also emerged as candidates for regulating survival of mesencephalic dopaminergic and sympathetic neurons. Interestingly, we have found that several bone morphogenetic proteins can be detected in developing embryonic day 14 rat dorsal root ganglia by means of reverse transcription-polymerase chain reaction and immunocytochemistry. To further elucidate their potential role during the period of ontogenetic neuron death, serum-free cultures of dorsal root sensory neurons from developing chick and rat embryos were treated with distinct bone morphogenetic proteins with or without simultaneous addition of other "established" neurotrophic factors. Our results show that bone morphogenetic proteins exert survival promoting effects on their own, and that they can positively modulate the effects of neurotrophins on sensory neurons. In particular, growth/differentiation factor-5, bone morphogenetic protein-2, -4, -7 and -12 significantly increased the survival promoting effects of neurotrophin-3 and nerve growth factor on cultured dorsal root ganglion neurons.These results fit well into the current concept that neurotrophic factors may act synergistically in ensuring neuronal survival. Moreover, these data suggest potential instructive interactions of bone morphogentic proteins and neurotrophins during sensory neuron development. Finally, the documented neurotrophic capacity of bone morphogenetic protein family members may have potential relevance for the treatment of peripheral neuropathies. (C) 1999 IBRO. Published by Elsevier Science Ltd.