Low (20 cGy) Doses of 1 GeV/u56Fe-Particle Radiation Lead to a Persistent Reduction in the Spatial Learning Ability of Rats

Britten, Richard A; Davis, Leslie K; Johnson, Angela M; Keeney, Sonia; Siegel, Andrew; Sanford, Larry D; Singletary, Sylvia J; Lonart, György

doi:10.1667/rr2637.1

Cited by 134Effects of Radiation ExposureSpaceflight effects on biologyRadiation Therapy and Dosimetry

Low (20 cGy) Doses of 1 GeV/u56Fe-Particle Radiation Lead to a Persistent Reduction in the Spatial Learning Ability of Rats

Britten, Richard A, Davis, Leslie K, Johnson, Angela M, Keeney, Sonia, Siegel, Andrew, Sanford, Larry D, Singletary, Sylvia J, Lonart, György·2012·Radiation Research

DOI 10.1667/rr2637.1

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Abstract

Exposure to galactic cosmic radiation (GCR) is considered to be a potential health risk in long-term space travel, and it represents a significant risk to the central nervous system (CNS). The most harmful component of GCR is the HZE [high-mass, highly charged (Z), high-energy] particles, e.g. (56)Fe. In previous ground-based experiments, exposure to high doses of HZE-particle radiation induced pronounced deficits in hippocampus-dependent learning and memory in rodents. Recent data suggest that glutamatergic transmission in hippocampal synaptosomes is impaired after low (60 cGy) doses of 1 GeV/u (56)Fe particles, which could lead to impairment of hippocampus-dependent spatial memory. To assess the effects of mission-relevant (20-60 cGy) doses of 1 GeV/u (56)Fe particles on hippocampus-dependent spatial memory, male Wistar rats either received sham treatment or were irradiated and tested 3 months later in the Barnes maze test. Compared to the controls, rats that received 20, 40 and 60 cGy 1 GeV/u (56)Fe particles showed significant impairments in their ability to locate the escape box in the Barnes maze, which was manifested by progressively increasing escape latency times over the 3 days of testing. However, this increase was not due to a lack of motivation of the rats to escape, because the total number of head pokes (and especially incorrect head pokes) remained constant over the test period. Given that rats exposed to X rays did not exhibit spatial memory impairments until >10 Gy was delivered, the RBE for 1 GeV/u (56)Fe-particle-induced hippocampal spatial memory impairment is ∼50. These data demonstrate that mission-relevant doses of 1 GeV/u (56)Fe particles can result in severe deficits in hippocampus-dependent neurocognitive tasks, and the extreme sensitivity of these processes to 1 GeV/u (56)Fe particles must arise due to the perturbation of multiple processes in addition to killing neuronal cells.

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Britten et al. have shown that doses as low as 20 cGy of simulated GCR radiation (1 GeV/u 56Fe particles) can significantly impair learning and memory in a rodent model.
“Britten et al. have shown that doses as low as 20 cGy of simulated GCR radiation (1 GeV/u 56Fe particles) can significantly impair learning and memory in a rodent model.”
From Space Radiation: The number one risk to astronaut health beyond low earth orbit (2014) · cites this paper as [55]
Mission-relevant doses of HZE particles may result in deficits in hippocampus-dependent neurocognitive tasks, most likely due to the perturbation of multiple processes, in addition to killing neuronal cells.
“These results demonstrate that mission-relevant doses of HZE particles may result in deficits in hippocampus-dependent neurocognitive tasks, most likely due to the perturbation of multiple processes, in addition to killing neuronal cells [55,56].”
From Space Radiation: The number one risk to astronaut health beyond low earth orbit (2014) · cites this paper as [55]

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Low (60 cGy) Doses of56Fe HZE-Particle Radiation Lead to a Persistent Reduction in the Glutamatergic Readily Releasable Pool in Rat Hippocampal Synaptosomes
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Executive Function in Rats is Impaired by Low (20 cGy) Doses of 1 GeV/u56Fe Particles
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Impaired Spatial Memory Performance in Adult Wistar Rats Exposed to Low (5–20 cGy) Doses of 1 GeV/n56Fe Particles
Britten, R. A., Jewell, J. S., Miller, V. D., Davis, L. K., Hadley, M. M., & Wyrobek, A. J. (2016) · Radiation Research · doi:10.1667/rr14120.1 · Cited by 42 · see citing works
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Spatial Memory Performance of Socially Mature Wistar Rats is Impaired after Exposure to Low (5 cGy) Doses of 1 GeV/n48Ti Particles
Britten, R. A., Jewell, J. S., Duncan, V. D., Davis, L. K., Hadley, M. M., & Wyrobek, A. J. (2017) · Radiation Research · doi:10.1667/rr14550.1 · Cited by 21 · see citing works
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Performance in hippocampus- and PFC-dependent cognitive domains are not concomitantly impaired in rats exposed to 20 cGy of 1 GeV/n 56Fe particles
Britten, R. A., Miller, V. D., Hadley, M. M., Jewell, J. S., & Macadat, E. (2016) · Life Sciences in Space Research · doi:10.1016/j.lssr.2016.06.005 · Cited by 23 · see citing works
Self-citation

Authors: Britten, R. A., Davis, L. K., Johnson, A. M., Keeney, S., Siegel, A., Sanford, L. D., Singletary, S. J., & Lonart, G.
Affiliations: Eastern Virginia Medical School (US)
ORCID: Britten, Richard A
Sanford, Larry D
Venue: Radiation Research
Publisher: Radiation Research Society
Published: 2012-02
Volume: 177
Issue: 2
Pages: 146-151
ISSN: 0033-7587 (ISSN-L)
1938-5404
DOI: 10.1667/rr2637.1
OpenAlex: W2097578302
Cited by: 134
References: 22
Citations by year: 2026: 2 · 2025: 3 · 2024: 4 · 2023: 12 · 2022: 5 · 2021: 13 · 2020: 12 · 2019: 13 · 2018: 15 · 2017: 12 · 2016: 9 · 2015: 11 · 2014: 15 · 2013: 5 · 2012: 3
FWCI: 8.21
Type: journal article
Language: en
Open access: closed
Locations: Radiation Research (publishedVersion)
PubMed (publishedVersion)
BioOne Complete (BioOne) (submittedVersion)
Funders: National Aeronautics and Space Administration
Brookhaven National Laboratory
Topics: Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
Health Sciences › Medicine › Physiology › Spaceflight effects on biology
Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Radiation Therapy and Dosimetry
Keywords: HZE particles, galactic cosmic rays, low-dose radiation effects, spatial learning impairment, Barnes maze, radiation-induced cognitive deficits, relative biological effectiveness, glutamatergic neurotransmission
MeSH terms: Animals, Cognition, Cosmic Radiation, Dose-Response Relationship, Radiation, Hippocampus, Male, Memory Disorders, Radiation Dosage, Rats, Wistar, Maze Learning, Rats

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Low (20 cGy) Doses of 1 GeV/u56Fe-Particle Radiation Lead to a Persistent Reduction in the Spatial Learning Ability of Rats

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