Galactic Cosmic Irradiation Alters Acute and Delayed Species-Typical Behavior in Male and Female Mice

Abstract

Exposure to space galactic cosmic radiation is a principal consideration for deep space missions. While the effects of space irradiation on the nervous system are not fully known, studies in animal models have shown that exposure to ionizing radiation can cause neuronal damage and lead to downstream cognitive and behavioral deficits. Cognitive health implications put humans and missions at risk, and with the upcoming Artemis missions in which female crew will play a major role, advance critical analysis of the neurological and performance responses of male and female rodents to space radiation is vital. Here, we tested the hypothesis that simulated Galactic Cosmic Radiation (GCRSim) exposure disrupts species-typical behavior in mice, including burrowing, rearing, grooming, and nest-building that depend upon hippocampal and medial prefrontal cortex circuitry. Behavior comprises a remarkably well-integrated representation of the biology of the whole animal that informs overall neural and physiological status, revealing functional impairment. We conducted a systematic dose-response analysis of mature (6-month-old) male and female mice exposed to either 5, 15, or 50 cGy 5-ion GCRSim (H, Si, He, O, Fe) at the NASA Space Radiation Laboratory (NSRL). Behavioral performance was evaluated at 72 h (acute) and 91-days (delayed) postradiation exposure. Specifically, species-typical behavior patterns comprising burrowing, rearing, and grooming as well as nest building were analyzed. A Neuroscore test battery (spontaneous activity, proprioception, vibrissae touch, limb symmetry, lateral turning, forelimb outstretching, and climbing) was performed at the acute timepoint to investigate early sensorimotor deficits postirradiation exposure. Nest construction, a measure of neurological and organizational function in rodents, was evaluated using a five-stage Likert scale ‘Deacon’ score that ranged from 1 (a low score where the Nestlet is untouched) to 5 (a high score where the Nestlet is completely shredded and shaped into a nest). Differential acute responses were observed in females relative to males with respect to species-typical behavior following 15 cGy exposure while delayed responses were observed in female grooming following 50 cGy exposure. Significant sex differences were observed at both timepoints in nest building. No deficits in sensorimotor behavior were observed via the Neuroscore. This study revealed subtle, sexually dimorphic GCRSim exposure effects on mouse behavior. Our analysis provides a clearer understanding of GCR dose effects on species typical, sensorimotor and organizational behaviors at acute and delayed timeframes postirradiation, thereby setting the stage for the identification of underlying cellular and molecular events.

The longitudinal behavioral effects of acute exposure to galactic cosmic radiation in female C57BL/6J mice: implications for deep space missions, female crews, and potential antioxidant countermeasures

“…A few studies have established that single particle type exposures lead to fine motor deficits in rats (Blackwell et al 2021), but differences in gross locomotion are scarce in the literature with some studies reporting that post-IRR OF locomotion is increased (Sorokina et al 2020;Kokhan et al 2019;Liu et al 2019;Boutros et al 2021), decreased (Allen et al 2015;Holshouser et al 2020), or unchanged (Impey et al 2023). Time post-IRR and dose may be important in seeing 5-ion (1H, 2 x 1,000 MeV/n; 4He, 400 MeV/n; 16O, 400 MeV/n; 28Si, 600 MeV/n) GCR-induced changes in locomotion (Puukila et al 2023), although there are conflicting results (Boutros et al 2021). The potential impact of time post-IRR on locomotion was one reason we examined this metric at several time points post-IRR.…”

“…Taken together, studies show single-ion, multi-ion, and even 33-GCR disturb a range of rodent central nervous system (CNS) functions, including memory, pattern separation, anxiety, vigilance, social novelty, and motor control (Kiffer et al 2019b;Cekanaviciute et al 2018;Clément et al 2020). However, narrowing these studies to just those that use multi-particle GCR (multi-ion, up to 33-GCR) highlights some contradictory results (Raber et al 2016;Kiffer et al 2018;Krukowski et al 2018a;Raber et al 2019;Kiffer et al 2020;Raber et al 2020;Klein et al 2021;Boutros et al 2021;Krukowski et al 2021;Raber et al 2021;Schaeffer et al 2022;Britten et al 2022;Puukila et al 2023;Alaghband et al 2023;Kiffer et al 2021). In addition, while most work has been performed in just male rodents, some of these studies show sex-specific outcomes of multi-ion whole-body exposure.…”