Short- and long-term effects of (56)Fe irradiation on cognition and hippocampal DNA methylation and gene expression.
Short- and long-term effects of (56)Fe irradiation on cognition and hippocampal DNA methylation and gene expression.
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（56）Fe照射对认知和海马DNA甲基化和基因表达的短期和长期影响。
DOI：
10.1186/s12864-016-3110-7
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发表时间：
2016-10-24
期刊：
影响因子：
4.4
通讯作者：
Raber J
中科院分区：
文献类型：
--
作者：
Impey S;Jopson T;Pelz C;Tafessu A;Fareh F;Zuloaga D;Marzulla T;Riparip LK;Stewart B;Rosi S;Turker MS;Raber J
宇航员在深空长时间执行任务期间和之后暴露在56Fe离子中，可能会对健康造成重大危害。我们之前的研究表明，在接受56Fe离子照射的2个月大的小鼠中，需要海马体的物体识别会受到影响，海马体是认知功能的关键结构。在这里，我们研究了6个月大的小鼠在56Fe离子照射下的物体识别能力，56Fe离子的生物年龄与宇航员的典型年龄更相关。此外，由于56Fe离子对海马功能有害影响的中介机制尚不清楚，我们研究了涉及突触可塑性和记忆、基因表达的海马网的变化，以及可能伴随基因表达变化的胞嘧啶甲基化(5mC)和羟甲基化(5hmC)的表观遗传学变化。我们评估了早期(2周)和晚期(20周)56Fe离子全身照射对海马依赖记忆和海马网稳定性的影响，以及这些影响是否与海马区DNA甲基化(5mC和5hmC)和基因表达的表观遗传学变化有关。在两周的时间点，0.1和0.4Gy射线照射后，物体识别和网络稳定性受到损害，但0.2Gy射线照射后，物体识别和网络稳定性没有受到影响。在20周的时间点上，在任何使用的照射剂量下，都没有看到物体识别或网络稳定性的损害。与这一模式一致，与2周时间点相比，20周时间点5hmC基因类别的路径重要性较低，尽管没有消除。同样，在2周的时间点观察到5mC基因通路的显著变化，但在20周的时间点没有观察到显著的基因类别。只有跟踪基因表达变化的5hmC变化。剂量和时间依赖的表观基因组重塑在56Fe离子暴露后的海马区与行为变化相关。本文的在线版本(doi：10.1186/s12864-0163110-7)包含补充材料，授权用户可以使用。
Astronauts are exposed to 56Fe ions that may pose a significant health hazard during and following prolonged missions in deep space. We showed previously that object recognition requiring the hippocampus, a structure critical for cognitive function, is affected in 2-month-old mice irradiated with 56Fe ions. Here we examined object recognition in 6-month-old mice irradiated with 56Fe ions, a biological age more relevant to the typical ages of astronauts. Moreover, because the mechanisms mediating the detrimental effects of 56Fe ions on hippocampal function are unclear, we examined changes in hippocampal networks involved in synaptic plasticity and memory, gene expression, and epigenetic changes in cytosine methylation (5mC) and hydroxymethylation (5hmC) that could accompany changes in gene expression. We assessed the effects of whole body 56Fe ion irradiation at early (2 weeks) and late (20 weeks) time points on hippocampus-dependent memory and hippocampal network stability, and whether these effects are associated with epigenetic changes in hippocampal DNA methylation (both 5mC and 5hmC) and gene expression. At the two-week time point, object recognition and network stability were impaired following irradiation at the 0.1 and 0.4 Gy dose, but not following irradiation at the 0.2 Gy dose. No impairments in object recognition or network stability were seen at the 20-week time point at any irradiation dose used. Consistent with this pattern, the significance of pathways for gene categories for 5hmC was lower, though not eliminated, at the 20-week time point compared to the 2-week time point. Similarly, significant changes were observed for 5mC gene pathways at the 2-week time point, but no significant gene categories were observed at the 20-week time point. Only the 5hmC changes tracked with gene expression changes. Dose- and time-dependent epigenomic remodeling in the hippocampus following 56Fe ion exposure correlates with behavioral changes. The online version of this article (doi:10.1186/s12864-016-3110-7) contains supplementary material, which is available to authorized users.
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影响因子：
4.4
作者：
Impey S;Pelz C;Tafessu A;Marzulla T;Turker MS;Raber J
通讯作者：
Raber J
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
DOI：
10.1523/jneurosci.1786-08.2008
发表时间：
2008-10-15
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Lubin FD;Roth TL;Sweatt JD
通讯作者：
Sweatt JD
影响因子：
14.9
作者：
Jin SG;Wu X;Li AX;Pfeifer GP
通讯作者：
Pfeifer GP
TET2 在中枢神经系统中的新功能：维持神经元存活
影响因子：
5.6
作者：
Mi Y;Gao X;Dai J;Ma Y;Xu L;Jin W
通讯作者：
Jin W