Food restriction can extend life span in rodents and was recently reported to increase the resistance of neurons in the brain to excitotoxic and metabolic insults. In principle, administration to ad libitum fed rodents of an agent that reduces glucose availability to cells should mimick certain aspects of food restriction. We now report that administration of 2-deoxy-D-glucose (2DG), a non-metabolizable analog of glucose, to adult rats results in a highly significant reduction in seizure-induced spatial memory deficits and hippocampal neuron loss. Pretreatment of rat hippocampal cell cultures with 2DG decreases the vulnerability of neurons to excitotoxic (glutamate) and oxidative (Fe2+) insults. The protective action of 2DG is associated with decreased levels of cellular oxidative stress and enhanced calcium homeostasis. 2DG treatment increased levels of the stress-responsive proteins GRP78 and HSP70 in hippocampal neurons, without affecting levels of Bcl-2 or GRP75, suggesting that mild reductions in glucose availability can increase neuronal resistance to oxidative and metabolic insults by a mechanism involving induction of stress proteins. Our findings establish cell culture and in vivo models of "chemical food restriction" which may prove useful in elucidating mechanisms of neuroprotection and in developing preventive approaches for neurodegenerative disorders that involve oxidative stress and excitotoxicity.

中文翻译：

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2-脱氧-D-葡萄糖保护海马神经元免受兴奋性毒性和氧化性损伤：应激蛋白参与的证据。

限制食物可以延长啮齿动物的寿命，最近有报道称它可以增加大脑神经元对兴奋性毒性和代谢损伤的抵抗力。原则上，对随意喂养的啮齿动物给药会降低细胞对葡萄糖的利用率的试剂应模仿食物限制的某些方面。我们现在报道，成年大鼠使用2-脱氧-D-葡萄糖（2DG），葡萄糖的一种不可代谢的类似物，会导致癫痫发作引起的空间记忆缺陷和海马神经元损失高度减少。用2DG预处理大鼠海马细胞培养物可降低神经元对兴奋性毒性（谷氨酸）和氧化性（Fe2 +）损伤的脆弱性。2DG的保护作用与降低细胞氧化应激水平和增强钙稳态有关。2DG处理可增加海马神经元中应激反应蛋白GRP78和HSP70的水平，而不会影响Bcl-2或GRP75的水平，表明葡萄糖可利用量的轻度降低可通过涉及诱导压力的机制增加神经元对氧化和代谢损伤的抵抗蛋白质。我们的发现建立了“化学食物限制”的细胞培养和体内模型，可用于阐明神经保护机制和开发针对涉及氧化应激和兴奋性毒性的神经退行性疾病的预防方法。提示葡萄糖可利用性的轻度降低可通过涉及诱导应激蛋白的机制增加神经元对氧化和代谢损伤的抵抗力。我们的发现建立了“化学食物限制”的细胞培养和体内模型，可用于阐明神经保护机制和开发针对涉及氧化应激和兴奋性毒性的神经退行性疾病的预防方法。提示葡萄糖可利用性的轻度降低可通过涉及诱导应激蛋白的机制增加神经元对氧化和代谢损伤的抵抗力。我们的发现建立了“化学食物限制”的细胞培养和体内模型，可用于阐明神经保护机制和开发针对涉及氧化应激和兴奋性毒性的神经退行性疾病的预防方法。