This study had the following specific aims:
The investigators confirmed the radiation-sensitivity of the CP, measuring significant cellular and molecular damage to the CP after exposure to X-ray and 56Fe radiation. The experiments include young and age-matched old reference groups to provide a means to distinguish between radiation effects and normal aging. The investigators discovered long-lived molecular signaling changes in the CNS after exposure to space radiation using transcriptomic, proteomic and metabolomics analyses of several brain regions (hippocampus, CP, CSF, and cortex) collected at ~3 days to ~21 months after whole body HZE or X-ray exposures (10-200cGy), usually for rats also tested on one or more psychometric assay. Expression profiling and bioinformatics identified a significant Huntington’s disease subnetwork and significant associations with neuroinflammation, oxidative stress, and various neurological diseases and neurocognitive dysfunctions.
The investigators demonstrated that cranial exposure of young adult rats to heavy particle ionizing radiation (HZE, 56Fe, and 12C) causes neurocognitive deficits that persist to very old age, that the magnitude of the deficits are variable across animals and was associated with molecular and cellular damage to the CP and hippocampus. At ~2 years after exposures, there were histological changes of the CP including occluded endothelial vessels, increases in the frequency of amyloid deposits throughout the CNS, and decreased epithelial expression of proteins that normally prevent amyloid fibril formation in CNS. In support of observation, the investigators found increased frequencies of amyloid plaques in exposed animals but noted that the increase in plaque frequency was delayed 4-9 months after exposure. These findings suggest that space radiation may increase the risks for Alzheimer-related pathologies in the brain, long after the exposure. The investigators also confirmed the hypothesis that radiation exposure damaged the ability of the CP to produce normal cerebral spinal fluid. Animals exposed to 10 and 100cGy 56Fe showed changes in many proteins associated with various neurological diseases, psychological disorders, neuronal cell death and survival. They also discovered molecular signaling changes that are associated with inter-individual variation in behavioral responses to HZE radiation, related to memory deficits and increased anxiety in rats.
In summary, this research in a rat model identified persistent histological and molecular defects in the various CNS tissues (CP, CSF, and hippocampus) that are different from normal aging and are associated with long-term neurocognitive dysfunction related to memory deficits, increased anxiety, and increased plaque formation long after HZE exposures.
No data sets are available. A final report was archived.
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