胰岛素样生长因子-I（IGF-I）和胶质细胞源性神经营养因子（GDNF）在完全挽救出生后运动神经元方面的相加作用和增强作用。
Additivity and potentiation of IGF-I and GDNF in the complete rescue of postnatal motor neurons.
作者信息
Bilak M M, Corse A M, Kuncl R W
机构信息
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21287-7519, USA.
出版信息
Amyotroph Lateral Scler Other Motor Neuron Disord. 2001 Jun;2(2):83-91. doi: 10.1080/146608201316949523.
BACKGROUND
Both growth and survival of motor neurons may depend on multiple neurotrophic factors. Individually, insulin-like growth factor I (IGF-I) and glial cell line-derived neurotrophic factor (GDNF) are potent neurotrophic/survival factors for postnatal motor neurons.
METHODS
We used an organotypic spinal cord model of glutamatergic degeneration in ALS to investigate whether IGF-I and GDNF interact to enhance motor neuron survival, their trophic effect on choline acetyltransferase (ChAT) activity, and their effect on neurite outgrowth.
RESULTS
We show that the combination of IGF-I and GDNF at active doses (1) is additively neuroprotective, (2) completely rescues rat motor neurons from chronic glutamate-mediated toxicity, and (3) additively upregulates motor neuron ChAT activity. Further, IGF-I, which by itself does not promote neurite outgrowth in this model, potentiates the neurite promoting action of GDNF.
CONCLUSION
The results predict that IGF-I combined with GDNF may provide a better therapy for the treatment of motor neuron disorders such as amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy.
背景
运动神经元的生长和存活可能依赖于多种神经营养因子。胰岛素样生长因子I（IGF-I）和胶质细胞源性神经营养因子（GDNF）单独而言都是出生后运动神经元强大的神经营养/存活因子。
方法
我们使用肌萎缩侧索硬化症（ALS）中谷氨酸能变性的脊髓器官型模型，来研究IGF-I和GDNF是否相互作用以增强运动神经元存活、它们对胆碱乙酰转移酶（ChAT）活性的营养作用以及它们对神经突生长的影响。
结果
我们发现活性剂量的IGF-I和GDNF组合（1）具有相加的神经保护作用，（2）能完全拯救大鼠运动神经元免受慢性谷氨酸介导的毒性，并且（3）能相加地上调运动神经元ChAT活性。此外，在该模型中自身并不促进神经突生长的IGF-I，能增强GDNF促进神经突生长的作用。
结论
这些结果预示，IGF-I与GDNF联合应用可能为治疗运动神经元疾病如肌萎缩侧索硬化症（ALS）和脊髓性肌萎缩症提供更好的治疗方法。
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