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Britten R.A.,Eastern Virginia Medical School | Davis L.K.,Eastern Virginia Medical School | Johnson A.M.,Eastern Virginia Medical School | Keeney S.,Eastern Virginia Medical School | And 4 more authors.
Radiation Research | Year: 2012

Exposure to galactic cosmic radiation (GCR) is considered to be a potential health risk in long-term space travel, and it represents a significant risk to the central nervous system (CNS). The most harmful component of GCR is the HZE [high-mass, highly charged (Z), high-energy] particles, e.g. 56Fe. In previous ground-based experiments, exposure to high doses of HZE-particle radiation induced pronounced deficits in hippocampus-dependent learning and memory in rodents. Recent data suggest that glutamatergic transmission in hippocampal synaptosomes is impaired after low (60 cGy) doses of 1 GeV/u 56Fe particles, which could lead to impairment of hippocampus-dependent spatial memory. To assess the effects of mission-relevant (2060 cGy) doses of 1 GeV/u 56Fe particles on hippocampus-dependent spatial memory, male Wistar rats either received sham treatment or were irradiated and tested 3 months later in the Barnes maze test. Compared to the controls, rats that received 20, 40 and 60 cGy 1 GeV/u 56Fe particles showed significant impairments in their ability to locate the escape box in the Barnes maze, which was manifested by progressively increasing escape latency times over the 3 days of testing. However, this increase was not due to a lack of motivation of the rats to escape, because the total number of head pokes (and especially incorrect head pokes) remained constant over the test period. Given that rats exposed to X rays did not exhibit spatial memory impairments until >10 Gy was delivered, the RBE for 1 GeV/u 56Fe-particle-induced hippocampal spatial memory impairment is ∼50. These data demonstrate that mission-relevant doses of 1 GeV/u 56Fe particles can result in severe deficits in hippocampus-dependent neurocognitive tasks, and the extreme sensitivity of these processes to 1 GeV/u 56Fe particles must arise due to the perturbation of multiple processes in addition to killing neuronal cells. © 2012 by Radiation Research Society. All rights of reproduction in any form reserved.


Lonart G.,Eastern Virginia Medical School | Parris B.,Eastern Virginia Medical School | Johnson A.M.,Eastern Virginia Medical School | Miles S.,Old Dominion University | And 3 more authors.
Radiation Research | Year: 2012

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., 56Fe 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 56Fe 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 56Fe 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 56Fe 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 56Fe 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. © 2012 by Radiation Research Society.


Graham T.W.,Veterinary Consulting Services | Breher E.,Veterinary Consulting Services | Farver T.B.,University of California at Davis | Cullor J.S.,University of California at Davis | And 2 more authors.
Journal of Animal Science | Year: 2010

Raising a heifer calf to reproductive age represents an enormous cost to the producer. Poor neonatal growth exacerbates the costs incurred for rearing, and use of blood variables that may be associated with poorly growing calves may offer predictive value for growth and performance. Thus, the principal objective of the present study was to describe changes in serum IGF-I, zinc, and copper from birth to 90 d in Holstein calves, while accounting for sex and twin status, in poorly growing calves and calves growing well. A second objective was to test the hypothesis that an association exists between these serum variables and morphometric indicators of growth. Measurements of BW, length, and height were recorded at birth and at 30, 60, and 90 d of age. Jugular blood (12 mL) was collected from each calf on d 1 to determine serum total protein, serum IgG, packed cell volume, serum zinc, serum copper, serum IGF-I, and CD18 genotype for bovine leukocyte adhesion deficiency; serum zinc, serum copper, and serum IGF-I (predictor variables) were also determined for each calf on d 2 through 10 and on d 30, 60, and 90. Stepwise multiple regression and logistic regression analyses were used to examine the relationships between the predictor variables and the dependent variables (BW, height, and length at d 30, 60, and 90 of life). Birth weight, sex, serum IGF-I (at all ages), serum copper, and the serum copper-to-zinc ratio were associated, to varying degrees, with the dependent growth variables. Birth weight was consistently the dominant predictor. In conclusion, these results suggest that lighter birth weight, reduced serum IGF-I, and inflammation may be important causes of poor growth in neonatal Holstein dairy calves. © 2010 American Society of Animal Science.


Britten R.A.,Eastern Virginia Medical School | Mitchell S.,Eastern Virginia Medical School | Johnson A.M.,Eastern Virginia Medical School | Singletary S.J.,Veterinary Consulting Services | And 6 more authors.
Health Physics | Year: 2010

In the event of a nuclear detonation, thousands of people will be exposed to non-lethal radiation doses. There are multiple long-term health concerns for exposed individuals who receive non-lethal radiation exposures. Low doses of radiation, especially of high linear energy transfer (LET) radiation, can lead to the development of neurocognitive defects. The identification of serum biomarkers that can be used to monitor the emergence of the long-term biological sequelae of radiation exposure, such as neurocognitive defects, would greatly help the post-exposure health monitoring of the affected population. The authors have determined the impact that cranial irradiation with 2 Gy of high LET (150 keV um-1) has on the ability of rats to perform spatial memory tasks, and identified serum protein changes that are biomarkers of radiation exposure and of radiation-induced neurocognitive impairment. Matrix Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectroscopy (MALDI TOF-TOF) analysis of weak cation exchange (WCX) enriched serum protein preparations identified 23 proteins of interest: 10 were biomarkers of physical radiation dose, with six showing increased expression and four being undetectable in the irradiated rat serum. Four proteins were uniquely expressed in those rats that had good spatial memory and nine proteins were markers of bad spatial memory. This study provides proof of the concept that serum protein profiling can be used to identify biomarkers of radiation exposure and the emergence of radiation-sequelae in this rat model, and this approach could be easily applied to other systems to identify radiation biomarkers. © 2010 Health Physics Society.

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