Van Den Bosch L, Robberecht W
Laboratory of Neurobiology, Department of Neurology, University of Leuven, Leuven, Belgium.
Brain Res Bull. 2000 Nov 1;53(4):383-8. doi: 10.1016/s0361-9230(00)00371-3.
We compared the effect of short and long exposures of cultured motor neurons to glutamate and kainate (KA) and studied the receptors involved in these two types of excitotoxicity. There was no difference in the receptor type used between short and long glutamate exposures as activation of the N-methyl-D-asparate (NMDA) receptor was in both cases responsible for the motor neuron death. Cell death through activation of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors only became apparent when desensitization of these receptors was prevented. In such conditions, motor neurons became much more sensitive to excitotoxicity, and activation of different types of AMPA receptors mediated motor neuron death after short, compared to long, exposures to the non-desensitizing AMPA receptor agonist, KA. Short KA exposures selectively affected motor neurons containing Ca(2+)-permeable AMPA receptors, as the KA effect was completely inhibited by Joro spider toxin and only motor neurons that were positive for the histochemical Co(2+) staining were killed. A long exposure to KA affected motor neurons through both Ca(2+)-permeable and Ca(2+)-impermeable AMPA receptors. The selective death of motor neurons vs. dorsal horn neurons was observed after short KA exposures indicating that the selective vulnerability of motor neurons to excitotoxicity is related to the presence of Ca(2+)-permeable AMPA receptors.
我们比较了培养的运动神经元短期和长期暴露于谷氨酸和 kainate（KA）的效果，并研究了参与这两种兴奋性毒性的受体。短期和长期谷氨酸暴露所使用的受体类型没有差异，因为在这两种情况下，N-甲基-D-天冬氨酸（NMDA）受体的激活都是运动神经元死亡的原因。只有当这些受体的脱敏被阻止时，通过α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体激活导致的细胞死亡才会显现出来。在这种情况下，运动神经元对兴奋性毒性变得更加敏感，与长期暴露相比，短期暴露于非脱敏性AMPA受体激动剂KA后，不同类型的AMPA受体激活介导了运动神经元死亡。短期KA暴露选择性地影响含有Ca(2+)通透型AMPA受体的运动神经元，因为KA的作用被Joro蜘蛛毒素完全抑制，只有组织化学Co(2+)染色呈阳性的运动神经元被杀死。长期暴露于KA通过Ca(2+)通透型和Ca(2+)非通透型AMPA受体影响运动神经元。短期KA暴露后观察到运动神经元与背角神经元的选择性死亡，这表明运动神经元对兴奋性毒性的选择性易感性与Ca(2+)通透型AMPA受体的存在有关。
