FURTHER CHARACTERIZATION OF THE EFFECTS OF BRAIN-DERIVED NEUROTROPHIC FACTOR AND CILIARY NEUROTROPHIC FACTOR ON AXOTOMIZED NEONATAL AND ADULT MAMMALIAN MOTOR-NEURONS
FURTHER CHARACTERIZATION OF THE EFFECTS OF BRAIN-DERIVED NEUROTROPHIC FACTOR AND CILIARY NEUROTROPHIC FACTOR ON AXOTOMIZED NEONATAL AND ADULT MAMMALIAN MOTOR-NEURONS
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DOI：
10.1002/cne.903420106
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发表时间：
1994-04-01
影响因子：
2.5
通讯作者：
KOLIATSOS, VE
中科院分区：
文献类型：
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作者：
CLATTERBUCK, RE;PRICE, DL;KOLIATSOS, VE
神经营养因子和神经细胞因子是两大类神经营养因子。据报道，睫状神经营养因子(CNTF)和脑源性神经营养因子(BDNF)可预防新生运动神经元轴突损伤后的变性。此外，BDNF在肌肉注射后被逆行运输到阿尔法运动神经元，BDNF在脊髓和肌肉中的表达模式表明该因子在运动神经元中具有生理作用。在本研究中，我们描述了脑源性神经营养因子对新生面运动神经元损伤的影响，并将这些观察扩展到成年运动神经元损伤模型(损伤诱导的腰椎运动神经元表型损伤)。尼氏染色结果显示，脑源性神经营养因子可减少神经切断所致的新生神经元变性55%(赋形剂治疗组存活神经元的百分比为25%；脑源性神经营养因子治疗组为80%)。被挽救的神经元具有完整的细胞器结构，但在电子显微镜下看起来较小，并有轻微的染色溶解。面神经近端辣根过氧化物酶(HRP)逆行标记显示，BDNF挽救的神经元具有完整的快速轴突运输机制。CNTF对新生运动神经元似乎没有明显的影响，但该因子缺乏疗效可能是由于其在应用部位的快速降解所致。脑源性神经营养因子不能逆转神经切断诱导的新生或成年动物递质标志物[乙酰胆碱合成酶胆碱乙酰转移酶(ChAT)或降解酶乙酰胆碱酯酶(AChE)]的减少，也不能逆转神经切断后成年运动神经元低亲和力神经营养素受体p75(NGFR)(神经生长因子受体)的上调。然而，BDNF似乎促进了受损的新生运动神经元中p75(NGFR)的表达。总之，本研究的结果表明，BDNF可以显著防止受损运动神经元的细胞死亡。然而，这种神经营养因子可能不是与运动神经元某些成熟特征的诱导和/或维持有关的逆行信号，特别是它们的递质表型。(C)1994年Wiley-Liss，Inc.
Neurotrophins and neural cytokines are two broad classes of neurotrophic factors. It has been reported that ciliary neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF) prevent the degeneration of axotomized neonatal motor neurons. In addition, BDNF is transported retrogradely to alpha-motor neurons following injection into the muscle, and patterns of BDNF expressed in spinal cord and muscle suggest a physiological role for this factor in motor neurons. In the present study, we characterize the effects of BDNF on axotomized neonatal facial motor neurons and extend these observations to adult models of motor neuron injury (axotomy-induced phenotypic injury of lumbar motor neurons). BDNF reduces axotomy-induced degeneration of neonatal neurons by 55% as determined by Nissl staining (percentage of surviving neurons in vehicle-treated cases, 25%; in BDNF-treated cases, 80%). Rescued neurons have an intact organelle structure but appear smaller and slightly chromatolytic on electron microscopic analysis. As demonstrated by intense retrograde labeling with horseradish peroxidase (HRP) applied to the proximal stump of the facial nerve, neurons rescued by BDNF have intact mechanisms of fast axonal transport. CNTF did not appear to have significant effects on neonatal motor neurons, but the lack of efficacy of this factor may be caused by its rapid degradation at the application site. BDNF is not capable of reversing the axotomy-induced reduction in transmitter markers [i.e., the acetylcholine-synthesizing enzyme choline acetyltransferase (ChAT) or the degrading enzyme acetylcholinesterase (AChE)] in neonatal or adult animals or the axotomy-induced up-regulation of the low-affinity neurotrophin receptor p75(NGFR) (nerve growth factor receptor) in adult motor neurons. However, BDNF appears to promote the expression of p75(NGFR) in injured neonatal motor neurons. In concert, the findings of the present study suggest that BDNF can significantly prevent cell death in injured motor neurons. However, this neurotrophin may not be a retrograde signal associated with the induction and/or maintenance of some mature features of motor neurons, particularly their transmitter phenotype. (C) 1994 Wiley-Liss, Inc.