title: Impaired Spatial Memory Performance in Adult Wistar Rats Exposed to Low (5-20 cGy) Doses of 1 GeV/n (56)Fe Particles.
abstract: Prolonged deep space missions to planets and asteroids will expose astronauts to galactic cosmic radiation, comprised of low-linear energy transfer (LET) ionizing radiations, high-energy protons and high-Z and energy (HZE) particles, such as (56)Fe nuclei. In prior studies with rodents exposed to HZE particle radiation at doses likely to be encountered during deep space missions (<20 cGy) investigators reported impaired hippocampal-dependent neurocognitive performance and further observed substantial variation among the irradiated animals in neurocognitive impairment, ranging from no observable effects to severe impairment. These findings point to the importance of incorporating quantitative measures of interindividual variations into next generation risk assessment models of radiation risks on neurocognition. In this study, 269 male proven breeder Wistar rats were exposed to 1 GeV/n (56)Fe at doses of 0, 5, 10, 15 and 20 cGy, and tested for spatial memory performance on the Barnes maze at three months after exposure. The radiation response data were compared using changes in mean cohort performance and by the proportion of poor responders using the performance benchmark of two standard deviations below the mean value among the sham-irradiated cohort. Acute exposures to mission-relevant doses of 1 GeV/n (56)Fe reduced the mean spatial memory performance at three months after exposure (P < 0.002) and increased the proportions of poor performers, 2- to 3-fold. However, a substantial fraction of animals in all exposure cohorts showed no detectable change in performance, compared to the distribution of sham-irradiated animals. Our findings suggest that individualized metrics of susceptibility or resistance to radiation-induce changes in neurocognitive performance will be advantageous to the development of probabilistic risk assessment models for HZE-induced neurocognitive impairment.
authors.affiliation: Departments of a   Radiation Oncology.|b   Microbiology and.|c   Leroy T. Canoles Jr. Cancer Center, Eastern Virginia Medical School, Norfolk, Virginia 23507; and.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Britten
authors.affiliation: Departments of a   Radiation Oncology.
authors.forename: Jessica S
authors.initials: JS
authors.lastname: Jewell
authors.affiliation: Departments of a   Radiation Oncology.
authors.forename: Vania D
authors.initials: VD
authors.lastname: Miller
authors.affiliation: Departments of a   Radiation Oncology.
authors.forename: Leslie K
authors.initials: LK
authors.lastname: Davis
authors.affiliation: Departments of a   Radiation Oncology.
authors.forename: Melissa M
authors.initials: MM
authors.lastname: Hadley
authors.affiliation: d   Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Wyrobek
mesh_terms: D000818:Animals; D003359:Cosmic Radiation; D004307:Dose-Response Relationship, Radiation; D006624:Hippocampus / Q000473:pathology / Q000528:radiation effects*; D006801:Humans; D018499:Linear Energy Transfer; D008297:Male; D008569:Memory Disorders / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D065852:Spatial Memory / Q000528:radiation effects*