Nano-scale simulation of neuronal damage by galactic cosmic rays.

The effects of realistic, deep space radiation environments on neuronal function remain largely unexplored.In silicomodeling studies of radiation-induced neuronal damage provide important quantitative information about physico-chemical processes that are not directly accessible through radiobiological experiments. Here, we present the first nano-scale computational analysis of broad-spectrum galactic cosmic ray irradiation in a realistic neuron geometry. We constructed thousands ofin silicorealizations of a CA1 pyramidal neuron, each with over 3500 stochastically generated dendritic spines. We simulated the entire 33 ion-energy beam spectrum currently in use at the NASA Space Radiation Laboratory galactic cosmic ray simulator (GCRSim) using the TOol for PArticle Simulation (TOPAS) and TOPAS-nBio Monte Carlo-based track structure simulation toolkits. We then assessed the resulting nano-scale dosimetry, physics processes, and fluence patterns. Additional comparisons were made to a simplified 6 ion-energy spectrum (SimGCRSim) also used in NASA experiments. For a neuronal absorbed dose of 0.5 Gy GCRSim, we report an average of 250 ± 10 ionizations per micrometer of dendritic length, and an additional 50 ± 10, 7 ± 2, and 4 ± 2 ionizations per mushroom, thin, and stubby spine, respectively. We show that neuronal energy deposition by proton andα-particle tracks declines approximately hyperbolically with increasing primary particle energy at mission-relevant energies. We demonstrate an inverted exponential relationship between dendritic segment irradiation probability and neuronal absorbed dose for each ion-energy beam. We also find that there are no significant differences in the average physical responses between the GCRSim and SimGCRSim spectra. To our knowledge, this is the first nano-scale simulation study of a realistic neuron geometry using the GCRSim and SimGCRSim spectra. These results may be used as inputs to theoretical models, aid in the interpretation of experimental results, and help guide future study designs.