Individual Differences in Attentional Deficits and Dopaminergic Protein Levels following Exposure to Proton Radiation

Abstract

To assess the possible neurobehavioral performance risks to astronauts from living in a space radiation environment during long-duration exploration missions, the effects of head-only proton irradiation (150 MeV/n) at low levels (25-50 cGy, approximating an astronaut's exposure during a 2-year planetary mission) were examined in adult male Long-Evans rats performing an analog of the human psychomotor vigilance test (PVT). The rodent version of PVT or rPVT tracks performance variables analogous to the human PVT, including selective attention/inattention, inhibitory control ("impulsivity") and psychomotor speed. Exposure to head-only proton radiation (25, 50, 100 or 200 cGy) disrupted rPVT performance (i.e., decreased accuracy, increased premature responding, elevated lapses in attention and slowed reaction times) over the 250 day testing period. However, the performance decrements only occurred in a subgroup of animals at each exposure level, that is, the severity of the rPVT performance deficit was unrelated to proton exposure level. Analysis of brain tissue from irradiated and control rats indicated that only rats with rPVT performance deficits displayed changes in the levels of the dopamine transporter and, to a lesser extent, the D₂ receptor. Additional animals trained to perform a line discrimination task measuring basic and reversal learning showed no behavioral effects over the same exposure levels, suggesting a specificity of the proton exposure effects to attentional deficits and supporting the rPVT as a sensitive neurobehavioral assay.

Metabolomic Profiling of Urine Samples from Mice Exposed to Protons Reveals Radiation Quality and Dose Specific Differences

“…As long term effects of exposure to space radiation persist and can lead to carcinogenesis and central nervous system effects, as has been previously demonstrated in mouse models (4, 5, 16, 17, 23–25), it is imperative to understand the early effects of radiation exposure and the metabolic changes that can contribute to genetic alterations through persistent inflammatory or oxidative responses. Urinary metabolomics can rapidly provide a snapshot of the metabolic state of an individual and as shown this first study of exposure to protons identify a significant number of metabolites that are involved in important biochemical processes.…”

Dose- and ApoE Isoform-Dependent Cognitive Injury after Cranial56Fe Irradiation in Female Mice

“…The most commonly employed tests include the Morris water maze and Barnes maze , novel object recognition, object in place recognition, (Casadesus et al 2004;Kumar et al 2013;Shukitt-Hale et al 2000;Tseng et al 2013), and contextual fear conditioning for hippocampus-dependent memory (especially spatial memory) but with strong associations with the cortex as well. Cognitive behaviors more closely associated with the frontal cortex include operant conditioning Rice et al 2009), attentional set shifting Lonart et al 2012), and psychomotor vigilance tests (Heinz et al 2008;Davis et al 2014). Anxiety and fear are commonly assessed with open field tests and elevated plus or zero mazes (Kumar et al 2013).…”

“…Reproduced from Figure 5 of . Davis et al (2014) exposed young Long-Evans rats to 25 -200 cGy head-only 150 MeV protons and tested them from 25 to 251 days post-irradiation using the rodent Psychomotor Vigilance Test (rPVT), which was adapted from a human test battery. The rPVT test uses light cues, nose-poke responses, and food rewards to measure reaction times, performance accuracy, persistence of attention, and impulsivity (premature responding) to randomized cues.…”

“…For example, Wistar rats have reduced granule cell projections to hippocampus CA3 compared with other strains (Ramirez-Amaya et al 2001). Of particular interest are the results from and Davis et al (2014) showing that cohorts of animals naturally stratify into high and low performers or groups that are sensitive or insensitive to radiation exposure with respect to highlevel cognitive performance. Some of the uncertainty in measurements based on population averages might be reduced by considering the possibility of stratification in performance within test samples.…”

Biological effects of space radiation and development of effective countermeasures

“…Examples of such publications include studies suggesting that the induction of Alzheimer’s disease may be a space radiation risk (42) and attention deficits may arise following exposure to low doses of space radiation (43). Many other publications have also indicated that there are major CNS space radiation risks [e.g., (44–52)].…”