The neuronal excitotoxicity that follows reoxygenation after a hypoxic period may contribute to epilepsy, Alzheimer's disease, Parkinson's disease and various disorders that are related to inadequate supplement of oxygen in neurons. Therefore, counteracting the deleterious effects of post-hypoxic stress is an interesting strategy to treat a large spectrum of neurodegenerative diseases. Here, we show that the expression of the key telomere protecting protein Trf2 decreases in the brain of mice submitted to a post-hypoxic stress. Moreover, downregulating the expression of n hippocampal neural cells of unchallenged mice triggers an excitotoxicity-like phenotype including glutamate overexpression and behavioral alterations while overexpressing in hippocampal neural cells of mice subjected to a post-hypoxic treatment prevents brain damages. Moreover, overexpression in culture neurons counteracts the oxidative stress triggered by glutamate. Finally, we provide evidence that the effect of downregulation on excitotoxicity involves repression leading to mitochondrial dysfunction. We propose that increasing the level of expression is a potential strategy to reduce post-hypoxic stress damages.

中文翻译：

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端粒因子TRF2在缺氧后脑损伤中的作用


缺氧期后复氧后的神经元兴奋性毒性可能导致癫痫、阿尔茨海默病、帕金森病以及与神经元供氧不足有关的各种疾病。因此，抵消缺氧后应激的有害影响是治疗多种神经退行性疾病的一种有趣的策略。在这里，我们发现，在缺氧后应激的小鼠大脑中，关键端粒保护蛋白 Trf2 的表达降低。此外，下调未受到攻击的小鼠海马神经细胞的表达会引发兴奋性毒性样表型，包括谷氨酸过度表达和行为改变，而在接受缺氧后治疗的小鼠海马神经细胞中过度表达可防止脑损伤。此外，培养神经元中的过度表达可以抵消谷氨酸引发的氧化应激。最后，我们提供的证据表明，下调对兴奋性毒性的影响涉及导致线粒体功能障碍的抑制。我们认为增加表达水平是减少缺氧应激损伤的潜在策略。