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. 2023 May 19;13(5):1214.
doi: 10.3390/life13051214.

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

Stephanie Puukila  1   2 , Olivia Siu  3   4 , Linda Rubinstein  5   6 , Candice G T Tahimic  2   7 , Moniece Lowe  2   8 , Steffy Tabares Ruiz  2   8 , Ivan Korostenskij  7 , Maya Semel  7 , Janani Iyer  2   5   9 , Siddhita D Mhatre  2   9 , Yasaman Shirazi-Fard  2 , Joshua S Alwood  2 , Amber M Paul  2   4   8 , April E Ronca  2   10
Affiliations

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

Stephanie Puukila et al. Life (Basel). .

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.

Keywords: GCR radiation exposure; cognition; rodent behavior; sex differences.

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Conflict of interest statement

The authors declare no conflict of interest. Research was sponsored by the National Aeronautics and Space Administration (NASA) through a contract with Oak Ridge Associated Universities. The views and conclusions contained in this document are those of the authors and should not be interpreted as representing the official policies, either expressed or implied, of the National Aeronautics and Space Administration (NASA) or the U.S. Government. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Neuroscore of C57Bl/6J male and female mice exposed to GCRSim. The total of seven tests (spontaneous activity, proprioception, vibrissae touch, limb symmetry, lateral turning, forelimb outstretching, and climbing) was evaluated. Neuroscore for male (A) and female (B) mice was evaluated 72 h post-GCRSim exposure of either 0 (sham), 5, 15, or 50 cGy. Data are presented as mean ± SD where n = 26.
Figure 2
Figure 2
The frequency of typical homecage behavior of C57Bl/6J male and female mice exposed to GCRSim. The total frequency of burrowing (A,B), rearing (C,D), and grooming (E,F) by male and female mice was evaluated in three-minute videos of undisturbed, homecage behavior. Timepoints include 72 h (acute) or 91 days (delayed) post-GCRSim exposure of either 0 (sham), 5, 15, or 50 cGy. Data are presented as individual points where n ≥ 13; significance where p < 0.05; # denotes dose effects significantly different than sham within that timepoint and * denotes significant difference between acute and delayed timepoints. One symbol denotes p < 0.05, two symbols denotes p < 0.01, and three symbols denotes p < 0.001.
Figure 3
Figure 3
The duration of typical homecage behavior of C57Bl/6J male and female mice exposed to GCRSim. The total duration of burrowing (A,B), rearing (C,D), and grooming (E,F) by male and female mice was evaluated in three-minute videos of undisturbed, homecage behavior. Timepoints include 72 h (acute) or 91 days (delayed) post-GCRSim exposure of either 0 (sham), 5, 15, or 50 cGy. Data are presented as individual points where n ≥ 13; significance where p < 0.05; # denotes dose effects significantly different than sham within that timepoint and * denotes significant difference between acute and delayed timepoints. One symbol denotes p < 0.05, three symbols denotes p < 0.001, and four symbols denotes p < 0.0001.
Figure 4
Figure 4
The total duration of movement of C57Bl/6J male and female mice exposed to GCRSim. The total movement duration of male (A) and female (B) mice was evaluated in 3 min videos of undisturbed, homecage behavior. Timepoints include 72 h (acute; C) or 91 days (delayed; D) post-GCRSim exposure of either 0 (sham), 5, 15, or 50 cGy. Data are presented as individual points where n ≥ 13; significance where p < 0.05; # denotes significant difference between sexes at that timepoint and * denotes significant difference between acute and delayed timepoints. Two symbols denotes p < 0.01, three symbols denotes p < 0.001, and four symbols denotes p < 0.0001.
Figure 5
Figure 5
Representative images of Deacon scores of observed Nestlet construction of C57Bl/6J male and female mice exposed to GCRSim. Nestlet construction was evaluated with the Deacon score. In this study, scores were either 3 (A), 4 (B), or 5 (C).
Figure 6
Figure 6
Deacon scores of Nestlet construction of C57Bl/6J male (A,C) and female (B,D) mice exposed to GCRSim. The Deacon score of Nestlet construction by male and female mice was evaluated in 3 min videos of undisturbed, homecage behavior. Timepoints include 72 h (acute) (A,B) or 91 days (delayed) (C,D) post-GCRSim exposure of either 0 (sham), 5, 15, or 50 cGy. Data are presented as frequency of each score where n ≥ 13; significance where p < 0.05; # denotes dose effects significantly different than sham within that timepoint and * denotes significant difference between acute and delayed timepoints. One symbol denotes p < 0.05.
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References

    1. Euston D.R., Gruber A.J., McNaughton B.L. The Role of Medial Prefrontal Cortex in Memory and Decision Making. Neuron. 2012;76:1057–1070. doi: 10.1016/j.neuron.2012.12.002. - DOI - PMC - PubMed
    1. Parihar V.K., Allen B., Tran K.K., Macaraeg T.G., Chu E.M., Kwok S.F., Chmielewski N.N., Craver B.M., Baulch J.E., Acharya M.M., et al. What Happens to Your Brain on the Way to Mars. Sci. Adv. 2015;1:e1400256. doi: 10.1126/sciadv.1400256. - DOI - PMC - PubMed
    1. Parihar V.K., Maroso M., Syage A., Allen B.D., Angulo M.C., Soltesz I., Limoli C.L. Persistent Nature of Alterations in Cognition and Neuronal Circuit Excitability after Exposure to Simulated Cosmic Radiation in Mice. Exp. Neurol. 2018;305:44–55. doi: 10.1016/j.expneurol.2018.03.009. - DOI - PubMed
    1. Raber J., Torres E.R.S., Akinyeke T., Lee J., Boutros S.J.W., Turker M.S., Kronenberg A. Detrimental Effects of Helium Ion Irradiation on Cognitive Performance and Cortical Levels of MAP-2 in B6D2F1 Mice. Int. J. Mol. Sci. 2018;19:1247. doi: 10.3390/ijms19041247. - DOI - PMC - PubMed
    1. Mhatre S.D., Iyer J., Puukila S., Paul A.M., Tahimic C.G.T., Rubinstein L., Lowe M., Alwood J.S., Sowa M.B., Bhattacharya S., et al. Neuro-Consequences of the Spaceflight Environment. Neurosci. Biobehav. Rev. 2022;132:908–935. doi: 10.1016/j.neubiorev.2021.09.055. - DOI - PubMed

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