NSC-34 Motor Neuron-Like Cells Are Unsuitable as Experimental Model for Glutamate-Mediated Excitotoxicity.
NSC-34 Motor Neuron-Like Cells Are Unsuitable as Experimental Model for Glutamate-Mediated Excitotoxicity.
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DOI：
10.3389/fncel.2016.00118
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发表时间：
2016
影响因子：
5.3
通讯作者：
Blasco H
中科院分区：
文献类型：
--
作者：
Madji Hounoum B;Vourc'h P;Felix R;Corcia P;Patin F;Guéguinou M;Potier-Cartereau M;Vandier C;Raoul C;Andres CR;Mavel S;Blasco H
在肌萎缩侧索硬化症(ALS)的发病机制中，谷氨酸诱导的兴奋性毒性是运动神经元变性的主要因素。脊髓-神经母细胞瘤杂交瘤细胞系(NSC-34)常被用作研究ALS生理病理机制的真实细胞模型。然而，NSC-34对谷氨酸的生理反应仍不充分。在这项研究中，我们评估了分化的NSC-34(NSC-34D)作为谷氨酸兴奋毒性研究的体外模型的相关性。NSC-34D具有运动神经元样细胞的形态和生理特性，并表达谷氨酸受体亚基GluA1-4、GluN1和GluN2A/D。尽管有这些不同的特性，但与运动神经元原代培养(MN)相反，谷氨酸对培养的NSC-34D的存活和形态没有特异的影响。此外，与原代MN相比，NSC-34D在谷氨酸作用后细胞内钙离子浓度有轻微的、非持续性的升高。我们的发现，再加上无法获得只含有分化细胞的培养，表明运动神经元样NSC-34细胞系不是研究谷氨酸诱导的兴奋毒性的合适的体外模型。我们认为，用原代培养的MN细胞比NSC-34细胞更适合于从细胞水平探讨谷氨酸介导的兴奋性毒性在ALS等运动神经元疾病中的发病机制。
Glutamate-induced excitotoxicity is a major contributor to motor neuron degeneration in the pathogenesis of amyotrophic lateral sclerosis (ALS). The spinal cord × Neuroblastoma hybrid cell line (NSC-34) is often used as a bona fide cellular model to investigate the physiopathological mechanisms of ALS. However, the physiological response of NSC-34 to glutamate remains insufficiently described. In this study, we evaluated the relevance of differentiated NSC-34 (NSC-34D) as an in vitro model for glutamate excitotoxicity studies. NSC-34D showed morphological and physiological properties of motor neuron-like cells and expressed glutamate receptor subunits GluA1–4, GluN1 and GluN2A/D. Despite these diverse characteristics, no specific effect of glutamate was observed on cultured NSC-34D survival and morphology, in contrast to what has been described in primary culture of motor neurons (MN). Moreover, a small non sustained increase in the concentration of intracellular calcium was observed in NSC-34D after exposure to glutamate compared to primary MN. Our findings, together with the inability to obtain cultures containing only differentiated cells, suggest that the motor neuron-like NSC-34 cell line is not a suitable in vitro model to study glutamate-induced excitotoxicity. We suggest that the use of primary cultures of MN is more suitable than NSC-34 cell line to explore the pathogenesis of glutamate-mediated excitotoxicity at the cellular level in ALS and other motor neuron diseases.