Assessing the biological consequences of living in the space radiation environment represents one of the highest priority areas of NASA research. Of critical importance is the need for an assessment of the vulnerabilities of the central nervous system (CNS) leading to functional neurobehavioral changes during long-term space missions, and the development of effective countermeasures to such risks. The present proposal addresses this need via the application of an animal model to:
1) monitor indices of circadian function (i.e., spontaneous locomotor activity, body temperature) over various time points following irradiation;
2) determine the degree to which changes in circadian function are correlated with the severity of behavioral deficits in a rat psychomotor vigilance task; and
3) examine the underlying neurochemical alterations that accompany these radiation-induced changes in circadian function and neurobehavioral performance.
Prior research has 1) identified rats that are sensitive to radiation-induced deficits in neurobehavioral function; 2) identified changes in the dopamine neurotransmitter systems of these radiation-sensitive rats; and 3) identified an increased inflammatory response in the brain from 1-14 days post-irradiation.
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The current proposal will determine how the immediate effects of irradiation impact subsequent neurobehavioral deficits by assessing physiological markers of circadian function that are sensitive to changes in immunological functions and the onset of pathophysiological states. Groups of animals with implanted biotelemetry transmitters will be trained on a rodent version of the human Psychomotor Vigilance Test (the rPVT) and exposed to radiation; fluctuations in spontaneous locomotor activity and body temperatures will be assessed immediately following exposure and tracked over time and compared to the neurobehavioral performances. Individual variations in these physiological responses following radiation will be assessed for use as possible biomarkers for radiation sensitivity resulting in neurobehavioral deficits. Likely mechanisms of damage to the CNS following radiation exposure will be examined using brain tissue, in addition to an examination of cytokine levels in blood and peripheral organ systems.
1.) Whole-body proton (150 MeV/n) exposure results in deficits in sustained attention individual rats, such that some irradiated rats do not show any performance changes. This radiation exposure also decreases spontaneous locomotor activity across the post-radiation period, even though animals maintain 24-hr periodicity.
2.) Whole-body oxygen ion (16O, 1000 MeV/n) exposure results in deficits in social odor recognition memory at 1 month post-radiation for doses at or above 5 cGy. These same doses also result in deficits in sustained attention in individual rats that are primarily associated with slowed response times at short "wait times" on the rPVT, i.e., longer responses times when the organism has little time to prepare for the stimulus. Social recognition deficits were found at 6 months following 1 cGy, 10 cGy, and 25 cGy (1000 MeV/n) exposure. The lack of deficits at 5 cGy (1000 MeV/n) at the 6 month time point is LET-dependent, such that exposure to 5 cGy at 350 MeV/n resulted in deficits at this time point. No radiation-induced changes were found the number of Ki67+ cells in the subventricular zone in 1-25 cGy exposed rats compared to sham controls. Irradiated rats also displayed decreased levels of spontaneous locomotor activity in the post-radiation period.
3.) Using chemogenetics, we have shown that the mPFC is involved in encoding the social odor stimulus. Further, irradiated rats are unable to encode this stimulus, which results in deficits in 24-hr social recognition.
Crew health and performance is critical to successful human exploration beyond low Earth orbit.
The Human Research Program (HRP) investigates and mitigates the highest risks to human health
and performance, providing essential countermeasures and technologies for human space exploration.
Risks include physiological and performance effects from hazards such as radiation, altered gravity,
and hostile environments, as well as unique challenges in medical support, human factors,
and behavioral health support. The HRP utilizes an Integrated Research Plan (IRP) to identify
the approach and research activities planned to address these risks, which are assigned to specific
Elements within the program. The Human Research Roadmap is the web-based tool for communicating the IRP content.
The Human Research Roadmap is located at: https://humanresearchroadmap.nasa.gov/
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for information of how this experiment is contributing to the HRP's path for risk reduction.