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评估脊髓神经元X神经母细胞瘤杂交细胞系NSC - 34作为神经毒性测试模型的情况。

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

作者信息

Durham H D, Dahrouge S, Cashman N R

机构信息

Montreal Neurological Institute, McGill University, Quebec, Canada.

出版信息

Neurotoxicology. 1993 Winter;14(4):387-95.

PMID:7909362
Abstract

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.

摘要

NSC - 34是一种杂交细胞系,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。培养物包含两种细胞群体:具有细胞分裂能力的小的未分化细胞,以及表达运动神经元许多特性的大的多核细胞。在将培养物暴露于已知对运动神经元具有神经毒性的一系列化学物质后,评估了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试剂有反应。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胞体和突起中神经丝的局灶性聚集。吡啶硫酮钠诱导突起肿胀和回缩。相比之下,NSC - 34不是研究影响突触传递试剂的良好模型。未获得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。使用该细胞系研究化学神经毒性的困难在于底物粘附性差、需要常规传代培养以及随着反复传代培养神经元表型表达发生变化。

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