Evaluation of the spinal cord neuron X neuroblastoma hybrid cell line NSC-34 as a model for neurotoxicity testing.

Evaluation of the spinal cord neuron X neuroblastoma hybrid cell line NSC-34 as a model for neurotoxicity testing.
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发表时间:
1993
期刊:
影响因子:
3.4
通讯作者:
H. Durham;S. Dahrouge;N. Cashman
H. Durham;S. Dahrouge;N. Cashman
中科院分区:
医学3区
文献类型:
--
作者:
H. Durham;S. Dahrouge;N. Cashman

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NSC-34是由富含运动神经元的胚胎小鼠脊髓细胞与小鼠神经母细胞瘤融合产生的杂交细胞系。培养物含有两种细胞群:具有细胞分裂能力的小的未分化细胞和表达运动神经元的许多特性的较大的多核细胞。在将培养物暴露于已知对运动神经元具有神经毒性的化学品的选择后,评价了NSC-34细胞作为神经毒性研究模型的效用。NSC-34对影响电压门控离子通道、细胞骨架组织和轴突运输的药剂有反应。动作电位产生对各种离子通道阻滞剂的敏感性与培养的原代运动神经元相似。2,5-己二酮诱导NSC-34的胞体和突起中神经丝的局灶性聚集。吡啶硫酮钠引起突起肿胀和收缩。相反,NSC-34不是研究影响突触传递的药物的良好模型。没有获得NSC-34细胞之间突触连接的电生理证据。暴露于1 mM谷氨酸对细胞形态或动作电位产生没有影响。使用这条线研究化学神经毒性的困难是基质粘附性差,需要常规传代培养和重复传代培养神经元表型表达的变化。
NSC-34 is a hybrid cell line produced by fusion of motor neuron enriched, embryonic mouse spinal cord cells with mouse neuroblastoma. Cultures contain two populations of cells: small, undifferentiated cells that have the capacity to undergo cell division and larger, multi-nucleate cells that express many properties of motor neurons. The utility of NSC-34 cells as a model for investigation of neurotoxicity was evaluated following exposure of cultures to a selection of chemicals known to be neurotoxic to motor neurons. NSC-34 responded to agents that affect voltage-gated ion channels, cytoskeletal organization and axonal transport. The sensitivity of action potential production to various ion channel blockers was similar to that in primary motor neurons in culture. 2,5-hexanedione induced focal aggregation of neurofilaments in perikarya and processes of NSC-34. Sodium pyridinethione induced swelling and retraction of processes. In contrast, NSC-34 was not a good model in which to investigate agents that affect synaptic transmission. No electrophysiological evidence of synaptic connections between NSC-34 cells was obtained. Exposure to 1 mM glutamate had no effect on cell morphology or action potential production. Difficulties in using this line to investigate chemical neurotoxicity were poor substrate adhesion, requirement for routine subculture and change in expression of the neuronal phenotype with repeated subculture.