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Title: Partial body exposures to HZE particles: role of oxidative stress in the disruption of neuronal function and cognitive performance

Author
item RABIN, BERNARD - University Of Maryland
item SWITZER, ROBERT III - Neuroscience Associates
item CAHOON, DANIELLE - Tufts University
item POULOSE, SHIBU - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item ROTTMAN, VICTORIA - University Of Maryland
item HURD, PATRICK - University Of Maryland
item WILLATS, LAUREN - University Of Maryland
item CACIOPPO, ALICIA - University Of Maryland
item CHIGURUPATI, SNIGDHA - University Of Maryland
item Shukitt-Hale, Barbara

Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 10/12/2018
Publication Date: 1/22/2019
Citation: Rabin, B.M., Switzer, R., Cahoon, D., Poulose, S.M., Rottman, V., Hurd, P., Willats, L., Cacioppo, A., Chigurupati, S., Shukitt Hale, B. 2019. Partial body exposures to HZE particles: role of oxidative stress in the disruption of neuronal function and cognitive performance [abstract]. 2019 NASA Human Research Program Investigators Workshop. Program #19331.

Interpretive Summary:

Technical Abstract: INTRODUCTION: Whole body and head-only exposures to heavy particles (HZE particles) produce changes in neuronal function and cognitive performance. Because cognitive performance depends upon the integrity of the central nervous system, it may be assumed that exposure of the head is necessary to produce the disruption of cognitive performance. However, if HZE particle-induced oxidative stress is the primary cause of the changes in neuronal function and the related disruption of cognitive performance, then location of the exposure (head or body) should not be a factor in the effectiveness of the irradiation on these endpoints. The present experiment was designed to further explore the relationship between the location of exposure and the changes in neuronal function and cognitive performance produced by exposure to HZE particles. METHODS: The subjects were 181 male Sprague-Dawley rats weighing 200-225g at the time of irradiation. The rats (n = 20/treatment) were given above threshold head-only or body-only exposures to 56Fe particles (1000 MeV/n [100 cGy] or 600 MeV/n [75 cGy]) or 48Ti particles (1100 MeV/n [75 cGy] or 500 MeV/n [50 cGy]) at the NASA Space Radiation Laboratory (NSRL). Control rats (0 cGy) were taken to the NSRL and placed in the restraining tubes, but not irradiated. Twenty-four hours following irradiation, five rats/treatment were sacrificed by decapitation for analysis of oxidative stress in hippocampus and frontal cortex. The remaining rats were shipped to University of Maryland Baltimore County (UMBC) for evaluation of cognitive performance (novel object recognition, novel spatial recognition and operant responding on an ascending fixed-ratio schedule) beginning 4-6 weeks after exposure. Following behavioral testing, 5 rats/treatment condition were euthanized with pentobarbital, the brains perfused with formalin/PBS and shipped to Neuroscience Associates for additional analyses of neuronal functioning. The cognitive performance of the remaining rats (n = 10/treatment condition) was retested for radiation-induced changes in cognitive performance 10 months following exposure. RESULTS: The results showed that the disruption of cognitive performance was not dependent upon the location of the exposure. Irradiation of either the head or the body produced equivalent changes in performance. The results were similar following exposure to either 56Fe or 48Ti particles. Overall, the effect of head-only or body-only exposures on measures of oxidative stress and antioxidant enzymes in frontal cortex and hippocampus was variable, depending upon the specific measure, the tissue, and the location of the irradiation. However, exposure of the head was not regularly more effective than body-only exposures and the changes in neurochemical measures did not always parallel the changes in cognitive performance. CONCLUSIONS: The results of this experiment indicate that exposure of either the head or the body is a sufficient condition for the disruption of cognitive performance by exposure to HZE particles. Exposure of either the head or the body is sufficient to produce oxidative stress and changes in oxidant and antioxidant proteins in the central nervous system. The relationship between HZE particle-induced changes in cognitive performance and oxidative stress remains to be established.