| POSTDOCTORAL FELLOWSHIP
Aim 1: To determine the degree to which radiation-induced deficits in neurobehavioral function differ as a function of basal dopaminergic tone.
Aim 2: To determine the radioprotective effectiveness of dietary flaxseed (FS) to mitigate the deleterious effects of low-dose proton radiation on neurobehavioral function.
Aim 3: To determine DAergic and inflammatory protein levels in radiation-induced, neurobehaviorally-impaired Fischer and Lewis rats and in radioprotectant-treated (FS) rats.
Aim 4: To assess functional changes in dopaminergic neurotransmission following head-only proton radiation using well-characterized dopamine receptor-mediated behaviors (i.e., DA agonist-induced yawning and hypothermia).
To assess the likelihood of space radiation producing changes in the central nervous system (CNS), neurobehavioral functions are being measured in rodents via an animal test analogous to 'vigilance' tests in humans. Cognitive neurobehavioral functions relevant to astronaut mission performance effectiveness are assessed with a rodent analog of the Psychomotor Vigilance Test (PVT) currently used in space analog environments and by astronauts aboard the International Space Station (ISS). Neurobehavioral functions examined include assessments of general motor function and speed, vigilance, memory, inhibitory control ('impulsivity'), timing, and motivation. Groups of PVT-trained animals with inherent differences in dopamine system function were exposed to radiation and then re-tested for up to 5 months post-exposure. In an additional study, separate groups of animals were given an experimental diet supplemented with flaxseed and underwent the same behavioral testing using the rPVT. Likely mechanisms of damage to the CNS following radiation exposure and flaxseed treatment are being examined using Western blotting of proteins relevant to neurotransmitter function and inflammation.
• Exposure to protons, 56Fe, or 28Si ions produces highly specific effects on vigilance that include a phenotypic individual differences effect in that only a subset of irradiated animals show neurobehavioral deficits (i.e., are radiation sensitive ).
• Deficits in rPVT performance are associated with changes in several proteins important for dopaminergic neurotransmission, such as tyrosine hydroxylase and the dopamine transporter, in the frontal and parietal cortices, two brain regions thought to regulate PVT performance in humans.
• Radiation-insensitive animals appear to have increased density and/or sensitivity of D3 receptors, while radiation-sensitive rats appear to have a decrease in these same receptors or possibly an increase in D2 receptor sensitivity or levels.
• d-Amphetamine dose dependently improves rPVT performance in rats displaying proton-induced deficits (i.e., radiation sensitive rats), while these same doses have no impact on sham control performance levels.
The key findings during this funding period further support the hypothesis that the dopamine system is sensitive to the effects of radiation exposure and is an important system underlying the behavioral deficits in radiation-sensitive rats.
Proposed research for the coming year
Behavioral pharmacology studies assessing the effects dopamine receptor agonists in rats pre- and post-exposure will be conducted. In addition, assessments of spontaneous locomotor activity and core body temperature in rPVT-trained rats will be recorded pre- and post-radiation to determine if any behavioral markers related to fatigue and/or inflammation are associated with radiation-induced deficits.