title: Individual variations in dose response for spatial memory learning among outbred wistar rats exposed from 5 to 20 cGy of (56) Fe particles.
abstract: Exposures of brain tissue to ionizing radiation can lead to persistent deficits in cognitive functions and behaviors. However, little is known about the quantitative relationships between exposure dose and neurological risks, especially for lower doses and among genetically diverse individuals. We investigated the dose relationship for spatial memory learning among genetically outbred male Wistar rats exposed to graded doses of (56) Fe particles (sham, 5, 10, 15, and 20 cGy; 1 GeV/n). Spatial memory learning was assessed on a Barnes maze using REL3 ratios measured at three months after exposure. Irradiated animals showed dose-dependent declines in spatial memory learning that were fit by a linear regression (P for slope <0.0002). The irradiated animals showed significantly impaired learning at 10 cGy exposures, no detectable learning between 10 and 15 cGy, and worsened performances between 15 and 20 cGy. The proportions of poor learners and the magnitude of their impairment were fit by linear regressions with doubling doses of ∼10 cGy. In contrast, there were no detectable deficits in learning among the good learners in this dose range. Our findings suggest that genetically diverse individuals can vary substantially in their spatial memory learning, and that exposures at low doses appear to preferentially impact poor learners. This hypothesis invites future investigations of the genetic and physiological mechanisms of inter-individual variations in brain function related to spatial memory learning after low-dose HZE radiation exposures and to determine whether it also applies to physical trauma to brain tissue and exposures to chemical neurotoxicants. Environ. Mol. Mutagen. 57:331-340, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, University of California, Berkeley, California.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Wyrobek
authors.affiliation: Department of Radiation Oncology, and the Leroy T. Canoles Jr. Cancer Center, Eastern Virginia Medical School, Norfolk, Virginia.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Britten
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000528:radiation effects*; D001921:Brain / Q000503:physiopathology / Q000528:radiation effects; D003359:Cosmic Radiation; D004307:Dose-Response Relationship, Radiation; D007504:Iron Radioisotopes; D016014:Linear Models; D008297:Male; D018782:Maze Learning / Q000528:radiation effects*; D011829:Radiation Dosage; D017208:Rats, Wistar; D065852:Spatial Memory / Q000528:radiation effects*; D014916:Whole-Body Irradiation
chemical_list: D007504:Iron Radioisotopes
keywords: 56Fe 1GeV/n; Barnes Maze; ESL, escape latency; HZE (high mass (Z) and high energy) particles; REL3 ratio (relative escape latency after 3 days of training); dose response; high linear energy transfer (LET) radiation; linearity; low dose; males; resistant; retired breeders; sensitive; socially mature; space radiation; spatial memory learning; susceptible