page_title: Central nervous system effects from radiation exposure during spaceflight
section_title: Computer models and systems biology analysis of central nervous system risks
hierarchical_section_title: Central nervous system effects from radiation exposure during spaceflight / Computer models and systems biology analysis of central nervous system risks
caption_attribution_description: Figure 6-9. Model of plaque formation and neuronal death in Alzheimer’s disease. From Edelstein-Keshet and Spiros, 2002&#160;: Top row: Formation of a plaque and death of neurons in the absence of glial cells, when fibrous amyloid is the only injurious influence. The simulation was run with no astrocytes or microglia, and the health of neurons was determined solely by the local fibrous amyloid. Shown above is a time sequence (left to right) of three stages in plaque development, at early, intermediate, and advanced stages. Density of fibrous deposit is represented by small dots and neuronal health by shading from white (healthy) to black (dead). Note radial symmetry due to simple diffusion. Bottom row: Effect of microglial removal of amyloid on plaque morphology. Note that microglia (small star-like shapes) are seen approaching the plaque (via chemotaxis to soluble amyloid, not shown). At a later stage, they have congregated at the plaque center, where they adhere to fibers. As a result of the removal of soluble and fibrous amyloid, the microglia lead to irregular plaque morphology. Size scale: In this figure, the distance between the small single dots (representing low-fiber deposits) is 10 mm. Similar results were obtained for a 10-fold scaling in the time scale of neuronal health dynamics. Other information Page 205
context_page_description: Travel outside the Earth's protective atmosphere, magnetosphere, and gravitational field can harm human health, and understanding such harm is essential for successful manned spaceflight. Potential effects on the central nervous system are particularly important. A vigorous ground-based cellular and animal model research program will help quantify the risk to the CNS from space radiation exposure on future long distance space missions and promote the development of optimized countermeasures.
  Possible acute and late risks to the CNS from galactic cosmic rays and solar proton events are a documented concern for human exploration of our solar system. In the past, the risks to the CNS of adults who were exposed to low to moderate doses of ionizing radiation have not been a major consideration. However, the heavy ion component of space radiation presents distinct biophysical challenges to cells and tissues as compared to the physical challenges that are presented by terrestrial forms of radiation.
context_section_description: Since human epidemiology and experimental data for CNS risks from space radiation are limited, mammalian models are essential tools for understanding the uncertainties of human risks. Cellular, tissue, and genetic animal models have been used in biological studies on the CNS using simulated space radiation. New technologies, such as three-dimensional cell cultures, microarrays, proteomics, and brain imaging, are used in systematic studies on CNS risks from different radiation types. According to biological data, mathematical models can be used to estimate the risks from space radiation.
  Systems biology approaches to Alzheimer's disease that consider the biochemical pathways that are important in CNS disease evolution have been developed by research that was funded outside NASA. Figure 6-8 shows a schematic of the biochemical pathways that are important in the development of Alzheimer's disease. The description of the interaction of space radiation within these pathways would be one approach to developing predictive models of space radiation risks. For example, if the pathways that were studied in animal models could be correlated with studies in humans who are suffering from Alzheimer's disease, an approach to describe risk that uses biochemical degrees-of-freedom could be pursued. Edelstein-Keshet and Spiros  have developed an in silico model of senile plaques that are related to Alzheimer's disease. In this model, the biochemical interactions among TNF, IL-1B, and IL-6 are described within several important cell populations, including astrocytes, microglia, and neurons. Further, in this model soluble amyloid causes microglial chemotaxis and activates IL-1B secretion. Figure 6-9 shows the results of the Edelstein-Keshet and Spiros model simulating plaque formation and neuronal death. Establishing links between space radiation-induced changes to the changes that are described in this approach can be pursued to develop an in silico model of Alzheimer's disease that results from space radiation.
  Figure 6-8.Molecular pathways important in Alzheimer's disease. From Kyoto Encyclopedia of Genes and Genomes. Copyrighted image located at http://www.genome.jp/kegg/pathway/hsa/hsa05010.html
  Other interesting candidate pathways that may be important in the regulation of radiation-induced degenerative CNS changes are signal transduction pathways that are regulated by Cdk5. Cdk5 is a kinase that plays a key role in neural development; its aberrant expression and activation are associated with neurodegenerative processes, including Alzheimer's disease. This kinase is up-regulated in neural cells following ionizing radiation exposure.
caption: Figure 6-9. Model of plaque formation and neuronal death in Alzheimer's disease. From Edelstein-Keshet and Spiros, 2002 : Top row: Formation of a plaque and death of neurons in the absence of glial cells, when fibrous amyloid is the only injurious influence. The simulation was run with no astrocytes or microglia, and the health of neurons was determined solely by the local fibrous amyloid. Shown above is a time sequence (left to right) of three stages in plaque development, at early, intermediate, and advanced stages. Density of fibrous deposit is represented by small dots and neuronal health by shading from white (healthy) to black (dead). Note radial symmetry due to simple diffusion. Bottom row: Effect of microglial removal of amyloid on plaque morphology. Note that microglia (small star-like shapes) are seen approaching the plaque (via chemotaxis to soluble amyloid, not shown). At a later stage, they have congregated at the plaque center, where they adhere to fibers. As a result of the removal of soluble and fibrous amyloid, the microglia lead to irregular plaque morphology. Size scale: In this figure, the distance between the small single dots (representing low-fiber deposits) is 10 mm. Similar results were obtained for a 10-fold scaling in the time scale of neuronal health dynamics.[71]
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