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首页> 外文期刊>Biochimica et biophysica acta. Molecular basis of disease: BBA >Presymptomatically applied AMPA receptor antagonist prevents calcium increase in vulnerable type of motor axon terminals of mice modeling amyotrophic lateral sclerosis
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Presymptomatically applied AMPA receptor antagonist prevents calcium increase in vulnerable type of motor axon terminals of mice modeling amyotrophic lateral sclerosis

机译：假设应用的AMPA受体拮抗剂可防止易受伤害的小鼠肌肉轴突终端的钙增加肌营养侧面硬化

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Increased intracellular calcium (Ca), which might be the consequence of an excess influx through Ca-permeable alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, plays a crucial role in degeneration of motor neurons. Previously we demonstrated that the presymptomatic application of AMPA receptor antagonist, talampanel, could reduce Ca elevation in spinal motor neurons of mice carrying the G93A mutation of superoxide dismutase 1 (SOD1), modeling amyotrophic lateral sclerosis (ALS). It remained to be examined whether the remote, functionally semi-autonomous motor axon terminals could be rescued from the Ca overload, or if the terminals, where the degeneration possibly starts, already experience intractable changes at early time points. Thus using electron microscopic techniques, we measured the Ca level of motor axon terminals in the interosseus muscle of the SOD1 mutant animals, which are prototypes of vulnerable nerve endings in ALS. In line with the results obtained in the perikarya, talampanel treatment could reduce Ca increase evoked by the presence of mutant SOD1 in the axon terminals if the treatment was started presymptomatically but not at ail early symptomatic stage. We also tested the Ca level in the cell bodies and axon terminals of the oculomotor neurons, which are resistant to the disease. Neither Ca increase, nor talampanel effect could be demonstrated at either time point. This is consistent with the observations that oculomotor neurons contain increased level of Ca buffer, which could reduce excess Ca load, and they also express glutamate receptor subunit type 2, which renders AMPA receptors impermeable to Ca.
机译：增加的细胞内钙（CA），这可能是通过Ca-渗水α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体过量流入的结果，在运动神经元的退化中起着至关重要的作用。此前，我们证明了AMPA受体拮抗剂，Talampanel的假设应用可以降低携带超氧化物歧化酶1（SOD1）的G93A突变的小鼠脊柱运动神经元中的Ca升高，肌萎缩侧硬化（ALS）。它仍然要检查遥控器是否可以从CA过载救出，或者如果终端可能开始的终端，则在可能开始的终端，已经在早期点处经历了棘手的变化。因此，使用电子显微技术，我们测量了SOD1突变动物的嵌段肌肉中的电动机轴线端子的CA水平，这是ALS中脆弱神经末梢的原型。符合在Perikarya中获得的结果，如果治疗在胰岛素术中开始但不适用于早期症状阶段，Talampanel治疗可以降低Talampanel治疗可以降低Ca增加通过轴突末端的突变体SOD1引起的Ca增加。我们还测试了对疾病的血管内神经元的细胞体和轴突终端中的Ca水平。在任何一个时间点都没有增加CA增加，也没有塔拉姆的效果。这是一致的，观察到血管运动神经元含有增加的Ca缓冲液水平，这可能减少过量的Ca载荷，并且它们还表达谷氨酸受体亚单位型2，其使AMPA受体不可渗透到CA.

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