Epigenetic determinants of space radiation-induced cognitive dysfunction.
Epigenetic determinants of space radiation-induced cognitive dysfunction.
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DOI：
10.1038/srep42885
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发表时间：
2017-02-21
影响因子：
4.6
通讯作者：
Baulch JE
中科院分区：
文献类型：
--
作者：
Acharya MM;Baddour AA;Kawashita T;Allen BD;Syage AR;Nguyen TH;Yoon N;Giedzinski E;Yu L;Parihar VK;Baulch JE
参与火星探险等深空任务的宇航员面临的危险之一是暴露在辐射中，这使他们面临严重认知功能障碍的风险。这些辐射引起的认知障碍伴随着功能和结构变化，包括氧化应激、神经炎症和神经元结构退化。决定中枢神经系统功能的分子机制是多方面的，目前还不清楚辐射如何诱导大脑的持续变化。认知功能的这些决定因素包括将辐射反应转化为改变的基因表达和细胞表型的神经表观遗传机制。在这项研究中，我们已经证明了表观遗传畸变和空间相关辐射对认知的不良影响之间的相关性。在认知受损的辐射小鼠中，我们观察到海马中5-甲基胞嘧啶和5-羟甲基胞嘧啶水平增加，这与DNA甲基化酶DNMT 3a、TET 1和TET 3水平增加相一致。通过使用5-iodotubercidin抑制甲基化，我们证明了辐射的表观遗传效应的改善。除了保护免受辐射的分子效应，5-iodotubercidin恢复了未受辐射的动物的行为表现。这项研究的结果建立了神经表观遗传机制显着有助于影响辐射大脑和认知的功能和结构变化的可能性。
Among the dangers to astronauts engaging in deep space missions such as a Mars expedition is exposure to radiations that put them at risk for severe cognitive dysfunction. These radiation-induced cognitive impairments are accompanied by functional and structural changes including oxidative stress, neuroinflammation, and degradation of neuronal architecture. The molecular mechanisms that dictate CNS function are multifaceted and it is unclear how irradiation induces persistent alterations in the brain. Among those determinants of cognitive function are neuroepigenetic mechanisms that translate radiation responses into altered gene expression and cellular phenotype. In this study, we have demonstrated a correlation between epigenetic aberrations and adverse effects of space relevant irradiation on cognition. In cognitively impaired irradiated mice we observed increased 5-methylcytosine and 5-hydroxymethylcytosine levels in the hippocampus that coincided with increased levels of the DNA methylating enzymes DNMT3a, TET1 and TET3. By inhibiting methylation using 5-iodotubercidin, we demonstrated amelioration of the epigenetic effects of irradiation. In addition to protecting against those molecular effects of irradiation, 5-iodotubercidin restored behavioral performance to that of unirradiated animals. The findings of this study establish the possibility that neuroepigenetic mechanisms significantly contribute to the functional and structural changes that affect the irradiated brain and cognition.