Abstract
The space extending beyond Earth’s magnetosphere is subject to a complex field of high-energy charged nuclei, which are capable of traversing spacecraft shielding and human tissues, inducing dense ionization events. The central nervous system is a major area of concern for astronauts who will be exposed to the deep-space radiation environment on a mission to Mars, as charged-particle radiation has been shown to elicit changes to the dendritic arbor within the hippocampus of rodents, and related cognitive-behavioral deficits. We exposed 6-month-old male mice to whole-body 1H (0.5 Gy; 150 MeV/n; 18–19 cGy/minute) and an hour later to 16O (0.1Gy; 600 MeV/n; 18–33 Gy/min) at NASA’s Space Radiation Laboratory as a galactic cosmic ray-relevant model. Animals were housed with bedding which provides cognitive enrichment. Mice were tested for cognitive behavior 9 months after exposure to elucidate late radiation effects. Radiation induced significant deficits in novel object recognition and short-term spatial memory (Y-maze). Additionally, we observed opposing morphological differences between the mature granular and pyramidal neurons throughout the hippocampus, with increased dendritic length in the dorsal dentate gyrus and reduced length and complexity in the CA1 subregion of the hippocampus. Dendritic spine analyses revealed a severe reduction in mushroom spine density throughout the hippocampus of irradiated animals. Finally, we detected no general effect of radiation on single-nucleotide polymorphisms in immediate early genes, and genes involved in inflammation but found a higher variant allele frequency in the antioxidants thioredoxin reductase 2 and 3 loci.
Highlights
NASA’s efforts to extend manned spaceflight beyond low-earth orbit in the near future for the first time since the Apollo era dawns a new age in space exploration
We have previously shown that a 0.6 Gy exposure to 1H + 16O within the same day induced short-term spatial memory deficits, as assessed by the Y-maze 3 months after exposure, and altered dendritic morphology in the hippocampus of male C57Bl/6J mice (Kiffer et al, 2018)
Discrimination ratios indicate animals’ ability to discern two objects presented in a behavioral paradigm, and can be interpreted as a measure of animals “remembering” or “forgetting” a novel object (Burke et al, 2010)
Summary
NASA’s efforts to extend manned spaceflight beyond low-earth orbit in the near future for the first time since the Apollo era dawns a new age in space exploration. Current plans involve lunar sortie missions followed by the deep-space gateway, where astronaut crews will be exposed to radiation, confinement, and microgravity for increasing durations-all leading to a manned mission to Mars, Late Effects of 1H + 16O targeted toward the late 2030s (Drake et al, 2010) This new age in space exploration brings new challenges for long-term life support as humans have never been exposed to the complex radiation environment of deep space for more than 13 days. The increased heliospheric magnetic fields observed during solar maximum act to “shield” incoming GCR-effectively reducing their fluence, by approximately one order of magnitude (Nelson, 2016) Because of these phenomena, predicting the exact dosage encountered on a mission to mars is not tangible. Protons deliver approximately 50–60%, neutrons 10–20%, and HZE particles 10–20% of the relative total organ dose (Gy) from GCR (Nelson et al, 2016)
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