Abstract
BackgroundAstronauts are exposed to 56Fe ions that may pose a significant health hazard during and following prolonged missions in deep space. We showed previously that object recognition requiring the hippocampus, a structure critical for cognitive function, is affected in 2-month-old mice irradiated with 56Fe ions. Here we examined object recognition in 6-month-old mice irradiated with 56Fe ions, a biological age more relevant to the typical ages of astronauts. Moreover, because the mechanisms mediating the detrimental effects of 56Fe ions on hippocampal function are unclear, we examined changes in hippocampal networks involved in synaptic plasticity and memory, gene expression, and epigenetic changes in cytosine methylation (5mC) and hydroxymethylation (5hmC) that could accompany changes in gene expression. We assessed the effects of whole body 56Fe ion irradiation at early (2 weeks) and late (20 weeks) time points on hippocampus-dependent memory and hippocampal network stability, and whether these effects are associated with epigenetic changes in hippocampal DNA methylation (both 5mC and 5hmC) and gene expression.ResultsAt the two-week time point, object recognition and network stability were impaired following irradiation at the 0.1 and 0.4 Gy dose, but not following irradiation at the 0.2 Gy dose. No impairments in object recognition or network stability were seen at the 20-week time point at any irradiation dose used. Consistent with this pattern, the significance of pathways for gene categories for 5hmC was lower, though not eliminated, at the 20-week time point compared to the 2-week time point. Similarly, significant changes were observed for 5mC gene pathways at the 2-week time point, but no significant gene categories were observed at the 20-week time point. Only the 5hmC changes tracked with gene expression changes.ConclusionsDose- and time-dependent epigenomic remodeling in the hippocampus following 56Fe ion exposure correlates with behavioral changes.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-3110-7) contains supplementary material, which is available to authorized users.
Highlights
Astronauts are exposed to 56Fe ions that may pose a significant health hazard during and following prolonged missions in deep space
When object recognition was assessed at the 2-week time point, detrimental effects of 56Fe ion irradiation were seen with a non-linear dose response (Fig. 1a)
The detrimental effects of 56Fe ion irradiation on object recognition were transient because all dose groups explored the novel object significantly more than the familiar one at the 20-week time point (Fig. 1b)
Summary
Astronauts are exposed to 56Fe ions that may pose a significant health hazard during and following prolonged missions in deep space. Because the mechanisms mediating the detrimental effects of 56Fe ions on hippocampal function are unclear, we examined changes in hippocampal networks involved in synaptic plasticity and memory, gene expression, and epigenetic changes in cytosine methylation (5mC) and hydroxymethylation (5hmC) that could accompany changes in gene expression. Impey et al BMC Genomics (2016) 17:825 memory is impaired in 2-month-old mice two weeks following 56Fe ion irradiation [22] and twelve weeks following irradiation with protons [23] It is unclear whether object recognition is sensitive to effects of charged particles in mice irradiated at 6 months of age, a biological age relevant to the typical ages of astronauts during space missions. The mechanisms mediating the detrimental effects of a charged particle exposure such as 56Fe ions on hippocampus-dependent cognitive function are not clear, but might be associated with changes in hippocampal networks involved in synaptic plasticity and memory. Two different cellular compartments (nuclear and cytoplasmic) can be clearly distinguished, providing means to identify which neurons were active during distinct behavioral experiences [27]
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