Browsing by Author "Shukitt-Hale, Barbara"
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Item Effects of exposure to ¹²C and ⁴He particles on cognitive performance of intact and ovariectomized female rats(Elsevier Ltd., 2019-07-10) Rabin, Bernard M.; Miller, Marshall G.; Larsen, Alison; Spadafora, Christina; Zolnerowich, Nicholas N.; Dell'Acqua, Lorraine A.; Shukitt-Hale, BarbaraExposure to the types of radiation encountered outside the magnetic field of the earth can disrupt cognitive performance. Exploratory class missions to other planets will include both male and female astronauts. Because estrogen can function as a neuroprotectant, it is possible that female astronauts may be less affected by exposure to space radiation than male astronauts. To evaluate the effectiveness of estrogen to protect against the disruption of cognitive performance by exposure to space radiation intact and ovariectomized female rats with estradiol or vehicle implants were tested on novel object performance and operant responding on an ascending fixed-ratio reinforcement schedule following exposure to ¹²C (290 MeV/n) or ⁴He (300 MeV/n) particles. The results indicated that exposure to carbon or helium particles did not disrupt cognitive performance in the intact rats. Estradiol implants in the ovariectomized subjects exacerbated the disruptive effects of space radiation on operant performance. Although estrogen does not appear to function as a neuroprotectant following exposure to space radiation, the present data suggest that intact females may be less responsive to the deleterious effects of exposure to space radiation on cognitive performance, possibly due to the effects of estrogen on cognitive performance.Item Effects of head-only or whole-body exposure to very low doses of ⁴ He (1000 MeV/n) particles on neuronal function and cognitive performance(Elsevier Ltd, 2019-02) M.Rabin, Bernard; M.Poulose, Shibu; Bielinski, Donna F.; Shukitt-Hale, BarbaraOn exploratory class missions, astronauts will be exposed to a range of heavy particles which vary in linear energy transfer (LET). Previous research has shown a direct relationship between particle LET and cognitive performance such that, as particle LET decreases the dose needed to affect cognitive performance also decreases. Because a significant portion of the total dose experienced by astronauts may be expected to come from exposure to low LET ⁴ He particles, it would be important to establish the threshold dose of ⁴ He particles that can produce changes in cognitive performance. The results indicated that changes in neuronal function and cognitive performance could be observed following both head-only and whole-body exposures to ⁴ He particles at doses as low as 0.01–0.025 cGy. These results, therefore, suggest the possibility that astronauts on exploratory class missions may be at a greater risk for HZE-induced deficits than previously anticipated.Item Effects of partial- or whole-body exposures to 56Fe particles on brain function and cognitive performance in rats(Elsevier, 2020-07-24) Cahoon, Danielle S.; Shukitt-Hale, Barbara; Bielinski, Donna F.; Hawkins, Elizabeth M.; Cacioppo, Alicia M.; Rabin, Bernard M.On exploratory class missions, such as a mission to Mars, astronauts will be exposed to particles of high energy and charge (HZE particles). Exposure to HZE particles produces changes in neuronal function and can disrupt cognitive performance. Cells throughout the entire body, not just the brain, will be impacted by these particles. To determine the possible effects that irradiation of the body might have on neuronal function and cognitive performance, rats were given head-only, body-only or whole-body exposures to 56Fe particles. Cognitive performance (novel object recognition, operant responding) was tested in one set of animals; changes in brain function (oxidative stress, neuroinflammation) was tested in a second set of rats. The results indicated that there were no consistent differences in either behavioral or neurochemical endpoints as a function of the location of the irradiation. These results suggest that radiation to the body can impact the brain, therefore it may be necessary to re-evaluate the estimates of the risk of HZE particle-induced changes in neuronal function and cognitive performance.Item Modeling Space Radiation Induced Cognitive Dysfunction Using Targeted And Non-Targeted Effects(2020-12-01) Shuryak, Igor; Brenner, David; Blattnig, Steven; Shukitt-Hale, Barbara; Rabin, BernardRadiation-induced cognitive dysfunction is increasingly recognized as an important risk for human exploration of distant planets. Mechanistically-motivated mathematical modeling helps to interpret and quantify this phenomenon. Here we considered two general mechanisms of ionizing radiation-induced damage: targeted effects (TE), caused by traversal of cells by ionizing tracks, and non-targeted effects (NTE), caused by responses of other cells to signals released by traversed cells. We compared the performances of 18 dose response model variants based on these concepts, fitted by robust nonlinear regression to a large published data set on novel object recognition testing in rats exposed to multiple space-relevant radiation types (H, C, O, Si, Ti and Fe ions), covering wide ranges of linear energy transfer (LET) (0.22-181 keV/µm) and dose (0.001-2 Gy). The strongest support (by Akaike information criterion) was found for an NTE+TE model where NTE saturate at low doses (~0.01 Gy) and occur at all tested LETs, whereas TE depend on dose linearly with a slope that increases with LET. The importance of NTE was also found by additional analyses of the data using quantile regression and random forests. These results suggest that NTE-based radiation effects on brain function are potentially important for astronaut health and for space mission risk assessments.