NEUROTROPHIC AGENTS PREVENT MOTONEURON DEATH FOLLOWING SCIATIC-NERVE SECTION IN THE NEONATAL MOUSE
NEUROTROPHIC AGENTS PREVENT MOTONEURON DEATH FOLLOWING SCIATIC-NERVE SECTION IN THE NEONATAL MOUSE
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DOI：
10.1002/neu.480250702
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发表时间：
1994-07-01
期刊：
影响因子：
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通讯作者：
HOUENOU, LJ
中科院分区：
文献类型：
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作者：
LI, LX;OPPENHEIM, RW;HOUENOU, LJ
我们研究了不同的神经营养因子和生长因子在发育中的小鼠脊髓中预防轴突切断诱导的运动神经元细胞死亡的能力。在出生后单侧切断小鼠坐骨神经后，大多数运动神经元（MN）的损失发生在第四腰段（L4）的外侧运动柱。在出生后第5天（PN）或之前进行手术后，发生了显著的轴突切断诱导的细胞死亡。相比之下，当在PN 10之后进行轴突切断时，没有发现显著的细胞损失。PN 2或PN 5的轴突切断导致术后7天L4运动神经元损失44%，术后10天运动神经元损失66%。在损伤部位植入预先浸泡在各种神经营养因子中的明胶海绵拯救了轴突切断的运动神经元。神经生长因子（NGF）、神经营养因子-4/5（NT-4/5）和睫状神经营养因子（CNTF）挽救了20%-30%的运动神经元，而脑源性神经营养因子（BDNF）、神经营养因子-3（NT-3）和胰岛素样生长因子1（IGF-1）几乎挽救了所有运动神经元免于轴突切断诱导的死亡。相比之下，血小板衍生生长因子（PDGF）-AA，PDGF-AB，碱性成纤维细胞生长因子（bFGF），白细胞介素（IL-6）对运动神经元存活轴突切断后无效。NGF、BDNF、NT-3、IGF-1和CNTF也可防止轴突切断术诱导的存活运动神经元萎缩。这些数据表明，小鼠腰运动神经元继续是脆弱的轴突切断约1周后出生，一些营养剂，包括神经营养因子，CNTF，和IGF-1，可以防止这些神经元轴突切断后死亡。我们的研究证实并扩展了以前的报告轴突切断诱导小鼠运动神经元死亡的时间过程和神经营养因子的生存促进作用。(C)1994年，John Wiley and Sons，Inc.
We have examined the ability of different neurotrophic and growth factors to prevent axotomy-induced motoneuron cell death in the developing mouse spinal cord. After postnatal unilateral section of the mouse sciatic nerve, most motoneuron (MN) loss occurs in the lateral motor column of the fourth lumbar segment (L4). Significant axotomy-induced cell death occurred after surgery performed on or before postnatal day (PN) 5. In contrast, no significant cell loss was found when axotomy was performed after PN10. axotomy on PN2 or PN5 resulted in a 44% loss of L4 motoneurons by 7 days, and a 66% loss of motoneurons by 10 days postsurgery. Implantation of gelfoam presoaked in various neurotrophic factors at the lesion site rescued axotomized motoneurons. Nerve growth factor (NGF), neurotrophin-4/5 (NT-4/5) and ciliary neurotrophic factor(CNTF) rescued 20%-30% of motoneurons, whereas brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and insulin-like growth factor 1 (IGF-1) rescued virtually all motoneurons from axotomy-induced death. By contrast, platelet-derived growth factor(PDGF)-AA, PDGF-AB, basic fibroblast growth factor (bFGF), and interleukin (IL-6) were ineffective on motoneuron survival following axotomy. NGF, BDNF, NT-3, IGF-1, and CNTF also prevented axotomy-induced atrophy of surviving motoneurons. These data show that mouse lumbar motoneurons continue to be vulnerable to axotomy up to about 1 week after birth and that a number of trophic agents, including the neurotrophins, CNTF, and IGF-1, can prevent the death of these neurons following axotomy. Our studies confirm and extend previous reports on the time course of axotomy-induced mouse motoneuron death and the survival promoting effects of neurotrophic factors. (C) 1994 John Wiley and Sons, Inc.