Wilson A M, Kriegstein A R
Department of Neurology and Neurological Sciences, Stanford University School of Medicine, CA 94305.
Brain Res. 1991 Feb 1;540(1-2):297-301. doi: 10.1016/0006-8993(91)90523-x.
Glutamate is an excitatory neurotransmitter in turtle and mammalian cortex. In high concentrations it is toxic to mammalian neurons and is an important mediator in the pathway that leads to neuronal death from anoxia. Turtle neurons are remarkably resistant to anoxic injury and we sought to determine whether part of this resistance could be attributed to the sensitivity of turtle neurons to glutamate toxicity. Embryonic turtle cortical neurons were grown for 25 days in dissociated cell culture using a modification of a method developed for murine cortical cell culture. Turtle neurons in dissociated culture were found to express glutamate receptors which include both N-methyl-D-aspartate (NMDA) and non-NMDA receptor types. Remarkably, these neurons survive 5 minute exposures to glutamate in concentrations up to 3 mM, doses 30 times the LD50 and 6 times the LD100 for mouse cortical neurons. Elucidating the mechanism for this resistance may suggest new strategies for brain protection.
谷氨酸是海龟和哺乳动物皮层中的一种兴奋性神经递质。高浓度时,它对哺乳动物神经元有毒性,并且是导致神经元因缺氧死亡的途径中的重要介质。海龟神经元对缺氧损伤具有显著抗性,我们试图确定这种抗性的部分原因是否可归因于海龟神经元对谷氨酸毒性的敏感性。采用一种为小鼠皮层细胞培养开发的方法的改进方法,将海龟胚胎皮层神经元在解离细胞培养中培养25天。发现在解离培养中的海龟神经元表达谷氨酸受体,其中包括N-甲基-D-天冬氨酸(NMDA)和非NMDA受体类型。值得注意的是,这些神经元在浓度高达3 mM的谷氨酸中暴露5分钟后仍能存活,该剂量是小鼠皮层神经元LD50的30倍和LD100的6倍。阐明这种抗性的机制可能会为脑保护提出新的策略。