Effects of Acute and Chronic Exposure to a Mixed Field of Neutrons and Photons and Single or Fractionated Simulated Galactic Cosmic Ray Exposure on Behavioral and Cognitive Performance in Mice

Abstract

During space missions, astronauts experience acute and chronic low-dose-rate radiation exposures. Given the clear gap of knowledge regarding such exposures, we assessed the effects acute and chronic exposure to a mixed field of neutrons and photons and single or fractionated simulated galactic cosmic ray exposure (GCRsim) on behavioral and cognitive performance in mice. In addition, we assessed the effects of an aspirin-containing diet in the presence and absence of chronic exposure to a mixed field of neutrons and photons. In C3H male mice, there were effects of acute radiation exposure on activity levels in the open field containing objects. In addition, there were radiation-aspirin interactions for effects of chronic radiation exposure on activity levels and measures of anxiety in the open field, and on activity levels in the open field containing objects. There were also detrimental effects of aspirin and chronic radiation exposure on the ability of mice to distinguish the familiar and novel object. Finally, there were effects of acute GCRsim on activity levels in the open field containing objects. Activity levels were lower in GCRsim than sham-irradiated mice. Thus, acute and chronic irradiation to a mixture of neutrons and photons and acute and fractionated GCRsim have differential effects on behavioral and cognitive performance of C3H mice. Within the limitations of our study design, aspirin does not appear to be a suitable countermeasure for effects of chronic exposure to space radiation on cognitive performance.

FIG. 1.

LET distributions of the high-LET component of the simulated GCR spectrum, provided at the NASA Space Radiation Laboratory (27) with that calculated for the neutron fields used in this work. (Published and modified, with permission, from the following: Norbury JW, Schimmerling W, Slaba TC, Azzam EI, Badavi FF, Baiocco G, et al. Galactic cosmic ray simulation at the NASA Space Radiation Laboratory. Life Sci Space Res (Amst) 2016; 8:38-51; and Borak TB, Heilbronn LH, Krumland N, Weil MM. Design and dosimetry of a facility to study health effects following exposures to fission neutrons at low dose rates for long durations. Int J Radiat Biol 2019:1-14. Epub ahead of print.)

FIG. 2.

Effects of acute exposure to a mixture of neutrons and photons on distance moved in the open field containing objects (panel A) and on contextual fear memory (panel B) of C3H mice. *P = 0.003; ^#P = 0.089.

FIG. 3.

Effects of chronic exposure to a mixture of neutrons and photons in the open field and object recognition tests. Panel A: Sham-irradiated mice on a standard lab chow diet moved more on day 2 than day 1. ***P = 0.001. Panel B: Sham-irradiated mice on a standard chow spent more time in the center of the open field on day 2 than day 1. *P < 0.05. Panel C: Chronic exposure to a mixture of neutrons and photons in the open field containing objects did not affect the activity of mice on a standard chow. Panel D: Sham-irradiated mice on a standard chow explored the familiar object more than the novel object. This was not seen in irradiated mice on a standard chow. **P = 0.003.

FIG. 4.

Effects of acute and fractionated GCRsim on distance moved in the open field containing objects (panel A), percentage time exploring the familiar and novel objects (panel B) and fear learning (panel C). Panel A: Mice exposed to acute GCRsim moved less than sham-irradiated mice *P = 0.003. Panel B: Animals that received acute GCRsim preferred the familiar object over the novel object. ***P < 0.001. Panel C: There was a trend towards reduced fear learning in mice that received fractionated versus acute GCRsim. ^#P = 0.078.