Quinolinate and kainate neurotoxicity in neostriatal cultures is potentiated by co-culturing with neocortical neurons.
Quinolinate and kainate neurotoxicity in neostriatal cultures is potentiated by co-culturing with neocortical neurons.
复制标题
新纹状体培养物中喹啉酸盐和红藻氨酸盐的神经毒性通过与新皮质神经元共培养而增强。
DOI：
10.1016/0006-8993(90)90636-p
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发表时间：
1990
期刊：
影响因子：
2.9
通讯作者：
Kitai,ST
中科院分区：
文献类型：
--
作者：
Galarraga,E;Surmeier,DJ;Kitai,ST
有人提出，兴奋性氨基酸(EAA)调节的紊乱可能是亨廷顿病新纹状体神经元丢失的基础。通过比较新皮质和新层共同培养与单独培养新纹状体神经元的EAA毒性，评价新皮质传入纤维在决定新纹状体神经元EAA敏感性中的作用。仅在培养中，EaS只产生了轻微的神经元损失。红藻氨酸往往是最有效的兴奋性毒素，在1 mM的浓度下暴露5分钟后，会产生大约30%的神经元损失。在共培养中，新纹状体神经元对EAA毒性的敏感性显著增强；在毫摩尔浓度下，红藻氨酸和喹啉的毒性增加了约两倍，在微摩尔浓度下，喹啉的毒性增加了8倍。EAA与N-甲基-D-天冬氨酸受体拮抗剂2-氨基-5-膦-戊酸共同孵育的结果表明，喹啉酸的毒性作用主要是由NMDA受体介导的，而不是海人藻氨酸。
It has been suggested that a disorder in the regulation of excitatory amino acids (EAA) may underlie the loss of neostriatal neurons seen in Huntington's disease. The role of neocortical afferent fibers in determining the EAA sensitivity of neostriatal neurons was assessed by comparing EAA toxicity in co-cultures of neocortex and neostratum with that of neostriatum alone. In culturesalone, EAAs produced only modest neuronal losses. Kainate, which tended to be the most potent excitotoxin, produced a loss of approximately 30% of the neurons after a 5-min exposure at a 1-mM concentration. In co-cultures, the sensitivity of neostriatal neurons to EAA toxicity was dramatically enhanced; toxicity was increased about two-fold for kainate and quinolinate at millimolar concentrations and as much as 8-fold for quinolinate at micromolar concentrations. The effects of EAA co-incubation with theN-methyl-d-aspartate (NMDA) receptor antagonist, 2-amino-5-phosphonovaleric acid, suggested that the toxic actions of quinolinate, but not kainate, were mediated largely by NMDA receptors.