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Epigenetic determinants of space radiation-induced cognitive dysfunction.
- Source :
-
Scientific reports [Sci Rep] 2017 Feb 21; Vol. 7, pp. 42885. Date of Electronic Publication: 2017 Feb 21. - Publication Year :
- 2017
-
Abstract
- 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.
- Subjects :
- 5-Methylcytosine analogs & derivatives
5-Methylcytosine metabolism
Adenosine Kinase antagonists & inhibitors
Adenosine Kinase metabolism
Animals
Behavior, Animal drug effects
Behavior, Animal radiation effects
Brain metabolism
DNA (Cytosine-5-)-Methyltransferases genetics
DNA (Cytosine-5-)-Methyltransferases metabolism
DNA Methylation drug effects
DNA Methylation radiation effects
DNA Methyltransferase 3A
DNA-Binding Proteins genetics
DNA-Binding Proteins metabolism
Dioxygenases
Hippocampus metabolism
Male
Mice
Mice, Inbred C57BL
Proto-Oncogene Proteins genetics
Proto-Oncogene Proteins metabolism
Tubercidin analogs & derivatives
Tubercidin pharmacology
Whole-Body Irradiation
Brain radiation effects
Epigenomics
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 7
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 28220892
- Full Text :
- https://doi.org/10.1038/srep42885