Abstract
The radiation fields in space define tangible risks to the health of astronauts, and significant work in rodent models has clearly shown a variety of exposure paradigms to compromise central nervous system (CNS) functionality. Despite our current knowledge, sex differences regarding the risks of space radiation exposure on cognitive function remain poorly understood, which is potentially problematic given that 30% of astronauts are women. While work from us and others have demonstrated pronounced cognitive decrements in male mice exposed to charged particle irradiation, here we show that female mice exhibit significant resistance to adverse neurocognitive effects of space radiation. The present findings indicate that male mice exposed to low doses (≤30 cGy) of energetic (400 MeV/n) helium ions (4He) show significantly higher levels of neuroinflammation and more extensive cognitive deficits than females. Twelve weeks following 4He ion exposure, irradiated male mice demonstrated significant deficits in object and place recognition memory accompanied by activation of microglia, marked upregulation of hippocampal Toll-like receptor 4 (TLR4), and increased expression of the pro-inflammatory marker high mobility group box 1 protein (HMGB1). Additionally, we determined that exposure to 4He ions caused a significant decline in the number of dendritic branch points and total dendritic length along with the hippocampus neurons in female mice. Interestingly, only male mice showed a significant decline of dendritic spine density following irradiation. These data indicate that fundamental differences in inflammatory cascades between male and female mice may drive divergent CNS radiation responses that differentially impact the structural plasticity of neurons and neurocognitive outcomes following cosmic radiation exposure.
Highlights
Galactic cosmic rays (GCR) and energetic solar particles pose a range of adverse health risks to astronauts
Our findings suggest that sex-dependent differences in the response to cosmic irradiation can be linked to an attenuation of neuroinflammation and oxidative stress in female mice, providing a plausible explanation for their resistance to the adverse neurocognitive effects of 4He exposure
Present findings indicate that females show a marked resistance to similar doses and do not exhibit the same level of behavioral deficits as observed in male mice following exposure to 4He ions
Summary
Galactic cosmic rays (GCR) and energetic solar particles pose a range of adverse health risks to astronauts. Measurements of the radiation fields in space have provided considerable information concerning the types, fluences, and energies of charged particles that contribute to the expected doses astronauts would incur within and beyond the Earth’s protective magnetosphere (Nelson, 2016). Cosmic Radiation-Induced Sex Differences for a roundtrip mission to Mars, total doses are not expected to exceed 0.4–5 Gy, where the majority (∼80%) of whole-body exposures will be due to lighter particles (e.g., protons and helium ions; Nelson, 2016). Terrestrial-based simulations of the space radiation environment have provided invaluable information concerning the biological effects of cosmic rays and have begun to identify how such exposures can compromise the functionality of the CNS (Cucinotta, 2014). Several studies have shown that simulated GCR exposures compromise dendritic complexity (Allen et al, 2015), cause long-term suppression of glutamatergic transmission and NR2A receptor levels in the hippocampus (Parihar et al, 2015b), and elicit persistent alterations in long-term potentiation and synaptic plasticity (Parihar et al, 2018) and increases in autophagy and prolonged oxidative stress (Hinzman et al, 2018)
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