Executive Function in Rats is Impaired by Low (20 cGy) Doses of 1 GeV/u (56)Fe Particles.
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.
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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. · 3.73 Impact Factor
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ABSTRACT: Aims: Redox homeostasis is critical in regulating the fate and function of multipotent cells in the CNS. Here we investigated whether low dose charged particle irradiation could elicit oxidative stress in neural stem and precursor cells and whether radiation-induced changes in redox metabolism would coincide with cognitive impairment. Results: Low doses (< 1 Gy) of charged particles caused an acute and persistent oxidative stress. Early after (< 1week) irradiation, increased levels of reactive oxygen and nitrogen species were generally dose responsive, but were less dependent on dose weeks to months thereafter. Exposure to ion fluences resulting in less than 1 ion traversal per cell was sufficient to elicit radiation-induced oxidative stress. Whole body irradiation triggered a compensatory response in the rodent brain that led to a significant increase in antioxidant capacity 2 weeks following exposure, before returning to background levels at week 4. Low dose irradiation was also found to significantly impair novel object recognition in mice 2 and 12 weeks following irradiation. Innovation: Data provides evidence that acute exposure of neural stem cells and the CNS to very low doses and fluences of charged particles can elicit a persisting oxidative stress lasting weeks to months that is associated with impaired cognition. Conclusions: Exposure to low doses of charged particles causes a persistent oxidative stress and cognitive impairment over protracted times. Data suggests that astronauts subjected to space radiation may develop a heightened risk for mission critical performance decrements in space, along with a risk of developing longer-term neurocognitive sequelae.Antioxidants & Redox Signaling 06/2013; · 8.20 Impact Factor