Executive Function in Rats is Impaired by Low (20 cGy) Doses of 1 GeV/u (56)Fe Particles.

a Department of Pathology and Anatomy.
Radiation Research (Impact Factor: 2.7). 08/2012; 178(4):289-94. DOI: 10.2307/41679874
Source: PubMed

ABSTRACT Exposure to galactic cosmic radiation is a potential health risk in long-term space travel and represents a significant risk to the central nervous system. The most harmful component of galactic cosmic radiation is the HZE [high mass, highly charged (Z), high energy] particles, e.g., (56)Fe particle. In previous ground-based experiments, exposure to doses of HZE-particle radiation that an astronaut will receive on a deep space mission (i.e., ∼20 cGy) resulted in pronounced deficits in hippocampus-dependent learning and memory in rodents. Neurocognitive tasks that are dependent upon other regions of the brain, such as the striatum, are also impaired after exposure to low HZE-particle doses. These data raise the possibility that neurocognitive tasks regulated by the prefrontal cortex could also be impaired after exposure to mission relevant HZE-particle doses, which may prevent astronauts from performing complex executive functions. To assess the effects of mission relevant (20 cGy) doses of 1 GeV/u (56)Fe particles on executive function, male Wistar rats received either sham treatment or were irradiated and tested 3 months later for their ability to perform attentional set shifting. Compared to the controls, rats that received 20 cGy of 1 GeV/u (56)Fe particles showed significant impairments in their ability to complete the attentional set-shifting test, with only 17% of irradiated rats completing all stages as opposed to 78% of the control rats. The majority of failures (60%) occurred at the first reversal stage, and half of the remaining animals failed at the extra-dimensional shift phase of the studies. The irradiated rats that managed to complete the tasks did so with approximately the same ease as did the control rats. These observations suggest that exposure to mission relevant doses of 1 GeV/u (56)Fe particles results in the loss of functionality in several regions of the cortex: medical prefrontal cortex, anterior cingulated cortex, posterior cingulated cortex and the basal forebrain. Our observation that 20 cGy of 1 GeV/u (56)Fe particles is sufficient to impair the ability of rats to conduct attentional set-shifting raises the possibility that astronauts on prolonged deep space exploratory missions could subsequently develop deficits in executive function.

1 Bookmark
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The present report describes an animal model for examining the effects of radiation on a range of neurocognitive functions in rodents that are similar to a number of basic human cognitive functions. Fourteen male Long-Evans rats were trained to perform an automated intra-dimensional set shifting task that consisted of their learning a basic discrimination between two stimulus shapes followed by more complex discrimination stages (e.g., a discrimination reversal, a compound discrimination, a compound reversal, a new shape discrimination, and an intra-dimensional stimulus discrimination reversal). One group of rats was exposed to head-only X-ray radiation (2.3 Gy at a dose rate of 1.9 Gy/min), while a second group received a sham-radiation exposure using the same anesthesia protocol. The irradiated group responded less, had elevated numbers of omitted trials, increased errors, and greater response latencies compared to the sham-irradiated control group. Additionally, social odor recognition memory was tested after radiation exposure by assessing the degree to which rats explored wooden beads impregnated with either their own odors or with the odors of novel, unfamiliar rats; however, no significant effects of radiation on social odor recognition memory were observed. These data suggest that rodent tasks assessing higher-level human cognitive domains are useful in examining the effects of radiation on the CNS, and may be applicable in approximating CNS risks from radiation exposure in clinical populations receiving whole brain irradiation.
    PLoS ONE 08/2014; 9(8):e104393. · 3.53 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: High charge and energy (HZE) particles are a main hazard of the space radiation environment. Uncertainty regarding their health effects is a limiting factor in the design of human exploration-class space missions, that is, missions beyond low earth orbit. Previous work has shown that HZE exposure increases cancer risk and elicits other aging-like phenomena in animal models. Here, we investigate how a single exposure to HZE particle radiation, early in life, influences the subsequent age-dependent evolution of oxidative stress and appearance of degenerative tissue changes. Embryos of the laboratory model organism, Oryzias latipes (Japanese medaka fish), were exposed to HZE particle radiation at doses overlapping the range of anticipated human exposure. A separate cohort was exposed to reference γ-radiation. Survival was monitored for 750 days, well beyond the median lifespan. The population was also sampled at intervals and liver tissue was subjected to histological and molecular analysis. HZE particle radiation dose and aging contributed synergistically to accumulation of lipid peroxidation products, which are a marker of chronic oxidative stress. This was mirrored by a decline in PPARGC1A mRNA, which encodes a transcriptional co-activator required for expression of oxidative stress defense genes and for mitochondrial maintenance. Consistent with chronic oxidative stress, mitochondria had an elongated and enlarged ultrastructure. Livers also had distinctive, cystic lesions. Depending on the endpoint, effects of γ-rays in the same dose range were either lesser or not detected. Results provide a quantitative and qualitative framework for understanding relative contributions of HZE particle radiation exposure and aging to chronic oxidative stress and tissue degeneration.
    PLoS ONE 01/2014; 9(11):e111362. · 3.53 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Projecting a vision for space radiobiological research necessitates understanding the nature of the space radiation environment and how radiation risks influence mission planning, timelines and operational decisions. Exposure to space radiation increases the risks of astronauts developing cancer, experiencing central nervous system (CNS) decrements, exhibiting degenerative tissue effects or developing acute radiation syndrome. One or more of these deleterious health effects could develop during future multi-year space exploration missions beyond low Earth orbit (LEO). Shielding is an effective countermeasure against solar particle events (SPEs), but is ineffective in protecting crew members from the biological impacts of fast moving, highly-charged galactic cosmic radiation (GCR) nuclei. Astronauts traveling on a protracted voyage to Mars may be exposed to SPE radiation events, overlaid on a more predictable flux of GCR. Therefore, ground-based research studies employing model organisms seeking to accurately mimic the biological effects of the space radiation environment must concatenate exposures to both proton and heavy ion sources. New techniques in genomics, proteomics, metabolomics and other "omics" areas should also be intelligently employed and correlated with phenotypic observations. This approach will more precisely elucidate the effects of space radiation on human physiology and aid in developing personalized radiological countermeasures for astronauts.
    Life : open access journal. 09/2014; 4(3):491-510.