Individual variations in dose response for spatial memory learning among outbred wistar rats exposed from 5 to 20 cGy of ⁵⁶Fe 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.

Multi-domain cognitive assessment of male mice shows space radiation is not harmful to high-level cognition and actually improves pattern separation

“…In conclusion, it is understandable that HZE particle exposure is presumed to have a negative influence on some lower and high-level cognitive functions, as many studies support this conclusion 12,14,33,40,98,99 . However, our study shows this is not universally true.…”

Multi-domain cognitive assessment of male mice reveals whole body exposure to space radiation is not detrimental to high-level cognition and actually improves pattern separation

“…In conclusion, it is understandable that HZE particle exposure is presumed to have a negative influence on some lower and high-level cognitive functions, as many studies support this conclusion (21,23,44,(149)(150)(151) . However, our study shows this is not universally true.…”

Understanding the Effects of Deep Space Radiation on Nervous System: The Role of Genetically Tractable Experimental Models

“…Interestingly, the studies performed in rodents showed a high inter-individual variability in HZE-induced neurobehavioral deficits. In particular, in the low-range dosage, deficits were particularly pronounced in a subgroup of poor-learner animals [43]. This result strongly suggests the involvement of individual genetic factors, although the specific involved loci were not investigated.…”

“…Analyses of rodent models have provided the most extensive evidence about the potential neurocognitive complications caused by GCR ( Table 1), which could affect skills critical for missions, as well as long-term neuro-psychological health [8,10,24]. Low doses (5-20 cGy) of 1 MeV/n 56 Fe particles lead to severe deficits of mean spatial memory performance in rats, three months after exposure [42][43][44]. Similar effects where obtained by irradiating rats with low doses of 48 Ti [65], supporting the notion that LET-dependency of neurocognitive impairment may be relatively independent of cell killing.…”