Epigenetic determinants of space radiation-induced cognitive dysfunction

被引：47

作者：

Acharya, Munjal M. ^{[1
]}

Baddour, Al Anoud D. ^{[1
]}

Kawashita, Takumi ^{[1
]}

Allen, Barrett D. ^{[1
]}

Syage, Amber R. ^{[1
]}

Nguyen, Thuan H. ^{[1
]}

Yoon, Nicole ^{[1
]}

Giedzinski, Erich ^{[1
]}

Yu, Liping ^{[1
]}

Parihar, Vipan K. ^{[1
]}

Baulch, Janet E. ^{[1
]}

机构：

[1] Univ Calif Irvine, Irvine, CA 92697 USA

来源：

SCIENTIFIC REPORTS | 2017年 / 7卷

关键词：

MEDIAL PREFRONTAL CORTEX; ACTIVE DNA DEMETHYLATION; METHYLATION; MEMORY; METHYLTRANSFERASES; IRRADIATION; BEHAVIOR; OBJECTS; DNMT3A; RATS;

D O I：

10.1038/srep42885

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：15

共 39 条

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