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Epigenetic determinants of space radiation-induced cognitive dysfunction
Munjal M Acharya1, Al Anoud D Baddour1, Takumi Kawashita1
1University of California Irvine, CA 92697, USA.
Scientific Reports
|February 22, 2017
Summary
Space radiation exposure poses risks to astronaut cognition. This study reveals that neuroepigenetic changes, specifically DNA methylation, contribute to radiation-induced cognitive dysfunction, and inhibiting these changes can restore cognitive function.
Area of Science:
- Neuroscience
- Space Medicine
- Epigenetics
Background:
- Deep space missions expose astronauts to radiation, risking severe cognitive dysfunction.
- Radiation-induced cognitive impairments involve neuroinflammation, oxidative stress, and neuronal damage.
- The precise molecular mechanisms driving persistent brain alterations post-irradiation remain unclear.
Purpose of the Study:
- To investigate the role of neuroepigenetic mechanisms in radiation-induced cognitive dysfunction.
- To identify specific epigenetic alterations in the hippocampus following space-relevant irradiation.
- To evaluate the therapeutic potential of inhibiting DNA methylation for mitigating radiation effects on cognition.
Main Methods:
- Irradiation of mice with space-relevant radiation.
- Assessment of cognitive performance using behavioral tests.
- Quantification of DNA methylation levels (5-methylcytosine, 5-hydroxymethylcytosine) and DNA methylating enzymes (DNMT3a, TET1, TET3) in the hippocampus.
- Administration of a methylation inhibitor (5-iodotubercidin) to assess its effects.
Main Results:
- Cognitively impaired irradiated mice exhibited increased hippocampal 5-methylcytosine and 5-hydroxymethylcytosine levels.
- Elevated levels of DNMT3a, TET1, and TET3 were observed in cognitively impaired irradiated mice.
- Inhibition of methylation with 5-iodotubercidin ameliorated epigenetic changes and restored cognitive performance to control levels.
Conclusions:
- Neuroepigenetic mechanisms, particularly DNA methylation alterations in the hippocampus, significantly contribute to cognitive dysfunction following irradiation.
- Targeting neuroepigenetic pathways, such as DNA methylation, offers a potential therapeutic strategy to protect astronaut cognition during deep space missions.
- This study establishes a link between epigenetic aberrations and the adverse cognitive effects of space radiation, highlighting a critical area for future research and countermeasures.
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