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首页> 外文期刊>The European Journal of Neuroscience >Excitotoxicity mediated by non-NMDA receptors causes distal axonopathy in long-term cultured spinal motor neurons.
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Excitotoxicity mediated by non-NMDA receptors causes distal axonopathy in long-term cultured spinal motor neurons.

机译：非NMDA受体介导的兴奋性毒性在长期培养的脊髓运动神经元中引起远端轴突病。

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摘要

Excitotoxicity has been implicated as a potential cause of neuronal degeneration in amyotrophic lateral sclerosis (ALS). It has not been clear how excitotoxic injury leads to the hallmark pathological changes of ALS, such as the abnormal accumulation of filamentous proteins in axons. We have investigated the effects of overactivation of excitatory receptors in rodent neurons maintained in long-term culture. Excitotoxicity, mediated principally via non-N-methyl-D-aspartate (NMDA) receptors, caused axonal swelling and accumulation of cytoskeletal proteins in the distal segments of the axons of cultured spinal, but not cortical, neurons. Axonopathy only occurred in spinal neurons maintained for 3 weeks in vitro, indicating that susceptibility to axonal pathology may be related to relative maturity of the neuron. Excitotoxic axonopathy was associated with the aberrant colocalization of phosphorylated and dephosphorylated neurofilament proteins, indicating that disruption to the regulation of phosphorylation of neurofilaments may lead to their abnormal accumulation. These data provide a strong link between excitotoxicity and the selective pattern of axonopathy of lower motor neurons that underlies neuronal dysfunction in ALS.
机译：兴奋性毒性被认为是肌萎缩性侧索硬化症（ALS）中神经元变性的潜在原因。尚不清楚兴奋性毒性损伤如何导致ALS的标志性病理变化，例如轴突中丝状蛋白的异常积聚。我们研究了长期培养的啮齿动物神经元中兴奋性受体过度活化的影响。兴奋性毒性主要通过非N-甲基-D-天冬氨酸（NMDA）受体介导，导致轴突肿胀和细胞骨架蛋白在培养的脊髓神经元轴突的远端节段中积累，而并非在皮质神经元中。轴突病变仅发生在体外维持3周的脊髓神经元中，这表明对轴突病理的敏感性可能与神经元的相对成熟有关。兴奋性轴突病与磷酸化和去磷酸化的神经丝蛋白的异常共定位有关，这表明对神经丝磷酸化调节的破坏可能导致其异常积累。这些数据提供了兴奋性毒性与下运动神经元轴突病变的选择性模式之间的紧密联系，后者是ALS神经元功能障碍的基础。

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