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首页> 外文期刊>Neurochemistry International: The International Journal for the Rapid Publication of Critical Reviews, Preliminary and Original Research Communications in Neurochemistry >DNQX-induced toxicity in cultured rat hippocampal neurons: an apparent AMPA receptor-independent effect?
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DNQX-induced toxicity in cultured rat hippocampal neurons: an apparent AMPA receptor-independent effect?

机译：DNQX对培养的大鼠海马神经元的毒性作用：明显的AMPA受体非依赖性作用吗？

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摘要

To evaluate the involvement of AMPA receptor activation in neuronal cell death and survival, rat hippocampal neurons in culture were treated with AMPA receptor antagonists. A 46 h treatment with 6,7-dinitroquinoxaline-2,3-dione (DNQX), added 2 h after cell plating, induces a dose-dependent neurotoxicity. Similar effects are also observed in more mature hippocampal neurons (treatment at 14 days in vitro). DNQX toxic effect is neuron-specific since cultured hippocampal glial cells are unaffected. Attempts to characterise the site of action of DNQX suggest that ionotropic glutamate receptors would not be implicated. Indeed, (i) other AMPA receptor antagonists are either ineffective or only moderately efficient in mimicking DNQX effects; (ii) AMPA alone or in the presence of cyclothiazide, as well as, other AMPA receptor agonists, do not reverse DNQX action; (iii) DNQX neurotoxicity is not likely to involve blockade of NMDA receptor glycine site, since this effect is neither mimicked by 7-chlorokynurenate nor reversed by D-serine. Thus, DNQX toxicity in cultured hippocampal neurons is apparently mediated through an ionotropic glutamate receptor-independent way.
机译：为了评估AMPA受体激活与神经元细胞死亡和存活的关系，用AMPA受体拮抗剂处理了培养的大鼠海马神经元。细胞铺板后2小时，用6,7-二硝基喹喔啉-2,3-二酮（DNQX）处理46小时，诱导了剂量依赖性神经毒性。在更成熟的海马神经元中也观察到了类似的效果（体外治疗14天）。 DNQX的毒性作用是神经元特异性的，因为培养的海马神经胶质细胞不受影响。尝试表征DNQX的作用部位表明，不牵涉离子型谷氨酸受体。确实，（i）其他AMPA受体拮抗剂在模仿DNQX效果方面无效或仅中等有效; （ii）单独使用AMPA或在存在环噻嗪以及其他AMPA受体激动剂的情况下，不会逆转DNQX的作用; （iii）DNQX的神经毒性不太可能涉及NMDA受体甘氨酸位点的阻断，因为这种作用既不能被7-氯尿嘧啶模拟，也不能被D-丝氨酸逆转。因此，培养的海马神经元中的DNQX毒性显然是通过非离子型谷氨酸受体的独立介导的。

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