Project Number: 8050-51000-084-08-I
Project Type: Interagency Reimbursable Agreement
Start Date: Apr 14, 2013
End Date: Apr 22, 2017
Evaluate the effects of exposure to low dose/low fluence HZE particles and protons, as a model of accelerated aging, on cognitive performance and the changes in neural functioning that mediate the changes in performance. Determine the effects of radiation exposure on generation of oxidative stress (OS) and inflammation, neuronal signaling molecules, gene expression and macroautophagy in brain regions that are involved in mediating cognitive performance (e.g., hippocampus, striatum). Evaluate the prevention of OS/inflammation by antioxidant/anti-inflammatory diets on changes in neuronal function and the disruption of neurocognitive performance by HZE particles and protons. Evaluate the interaction between aging and radiation.
Use behavioral and neurochemical measures that have been previously shown to be sensitive to exposure to HZE particles and which may provide a basis for defining the risks of exposure to heavy particles on brain functioning and related behavior, similar to what is seen in aging. Thus, we will characterize the effects of exposure to HZE particles and protons on cognitive/behavioral endpoints and elucidate their relationship to changes in neural functioning as a function of time since irradiation. The first series of experiments will evaluate the effects of exposure to different particles and patterns of exposure (fractionation and combinations of particles) on specific behavioral and neuronal endpoints (Aims 1 and 2), both in terms of immediate and longer-term effects which may reflect degenerative processes initiated by exposure to HZE particles. We hypothesize that 1) Exposure to HZE particles and protons will produce oxidative stress (OS) and changes in inflammation, neuronal signaling molecules, gene expression and macroautophagy in brain regions that are involved in mediating cognitive performance (e.g., hippocampus, striatum). Furthermore, the dose of HZE particles needed to disrupt neurocognitive performance will be correlated with the amount of oxidative stress and inflammation and prevention of OS by antioxidant/anti-inflammatory (berry) diets will prevent the changes in neuronal function and the disruption of neurocognitive performance by HZE particles and protons; and 2) Exposure to low fluence HZE particles and protons will produce progressive degenerative changes in neurocognitive performance as a function of the time since irradiation. The second series of experiments (Aim 3) will evaluate the degree to which the characteristics of the individual, such as age or stroke-risk, modulate the effects of exposure to HZE particles.