Project Number: 8050-51000-102-03-A
Project Type: Cooperative Agreement
Start Date: Nov 15, 2016
End Date: Jul 1, 2021
Previous research in our laboratories has shown that exposure to particles of high energy and charge (HZE particles) and protons disrupts cognitive functioning and behavior, and causes oxidative stress, inflammation, and loss of autophagy function in critical regions of the brain such as striatum, hippocampus and cortex. However, the effects of exposure to multiple, subthreshold doses of the same or different particles or protons have not been extensively studied. The additional research detailed in this proposal will further define the nature of the interaction between age and sex and exposure to HZE particles and protons. Objective 1: Determine the conditions under which repeated subthreshold exposures to HZE particles and protons will affect neuronal function and cognitive performance. Objective 2: Evaluate the role of individual age and sex characteristics on the responsiveness of the organism to the effects of exposure to NASA-relevant doses of HZE particles and protons on neurocognitive and neuronal function.
For Objective 1, two month old, male SD rats will be irradiated with multiple subthreshold doses of protons of the isotope 4Helium. For Objective 2, male and female F344 rats ages 2, 6, 12, and 16mo will be castrated/ovariectomized and implanted with silastic tubing containing either gonadal hormones (testosterone/estradiol) or vehicle before being irradiated with 4He. Further experiments will use other components of the cosmic ray spectrum. Behavioral assessment of irradiated rats will test for learning and memory measured using novel object recognition and the Morris water and radial arm mazes. Fine motor coordination will be assessed using the accelerating rotarod. Rats will be sacrificed and brain regions, including hippocampus, cortex, and striatum, will be dissected and assessed for changes in biomarkers of oxidative stress, inflammatory, and autophagy using immunohistochemical and immunoblotting techniques.