Late Effects of (1)H + (16)O on Short-Term and Object Memory, Hippocampal Dendritic Morphology and Mutagenesis.

The space extending beyond Earth's magnetosphere is subject to a complex field of high-energy charged nuclei, which are capable of traversing spacecraft shielding and human tissues, inducing dense ionization events. The central nervous system is a major area of concern for astronauts who will be exposed to the deep-space radiation environment on a mission to Mars, as charged-particle radiation has been shown to elicit changes to the dendritic arbor within the hippocampus of rodents, and related cognitive-behavioral deficits. We exposed 6-month-old male mice to whole-body 1H (0.5 Gy; 150 MeV/n; 18-19 cGy/minute) and an hour later to 16O (0.1Gy; 600 MeV/n; 18-33 Gy/min) at NASA's Space Radiation Laboratory as a galactic cosmic ray-relevant model. Animals were housed with bedding which provides cognitive enrichment. Mice were tested for cognitive behavior 9 months after exposure to elucidate late radiation effects. Radiation induced significant deficits in novel object recognition and short-term spatial memory (Y-maze). Additionally, we observed opposing morphological differences between the mature granular and pyramidal neurons throughout the hippocampus, with increased dendritic length in the dorsal dentate gyrus and reduced length and complexity in the CA1 subregion of the hippocampus. Dendritic spine analyses revealed a severe reduction in mushroom spine density throughout the hippocampus of irradiated animals. Finally, we detected no general effect of radiation on single-nucleotide polymorphisms in immediate early genes, and genes involved in inflammation but found a higher variant allele frequency in the antioxidants thioredoxin reductase 2 and 3 loci.

Kiffer F ，Alexander T ，Anderson J ，Groves T ，McElroy T ，Wang J ，Sridharan V ，Bauer M ，Boerma M ，Allen A ... -  《Frontiers in Behavioral Neuroscience》

Late Effects of (16)O-Particle Radiation on Female Social and Cognitive Behavior and Hippocampal Physiology.

Kiffer F ，Alexander T ，Anderson JE ，Groves T ，Wang J ，Sridharan V ，Boerma M ，Allen AR ... -  《-》

Effects of (16)O charged-particle irradiation on cognition, hippocampal morphology and mutagenesis in female mice.

The effects of radiation in space on human cognition are a growing concern for NASA scientists and astronauts as the possibility for long-duration missions to Mars becomes more tangible. Oxygen (16O) radiation is of utmost interest considering that astronauts will interact with this radiation frequently. 16O radiation is a class of galactic cosmic ray (GCR) radiation and also present within spacecrafts. Whole-body exposure to high linear energy transfer (LET) radiation has been shown to affect hippocampal-dependent cognition. To assess the effects of high-LET radiation, we gave 6-month-old female C57BL/6 mice whole-body exposure to 16O at 0.25 or 0.1 Gy at NASA's Space Radiation Laboratory. Three months following irradiation, animals were tested for cognitive performance using the Y-maze and Novel Object Recognition paradigms. Our behavioral data shows that 16O radiation significantly impairs object memory but not spatial memory. Also, dendritic morphology characterized by the Sholl analysis showed that 16O radiation significantly decreased dendritic branch points, ends, length, and complexity in 0.1 Gy and 0.25 Gy dosages. Finally, we found no significant effect of radiation on single nucleotide polymorphisms in hippocampal genes related to oxidative stress, inflammation, and immediate early genes. Our data suggest exposure to heavy ion 16O radiation modulates hippocampal neurons and induces behavioral deficits at a time point of three months after exposure in female mice.

Swinton C ，Kiffer F ，McElroy T ，Wang J ，Sridharan V ，Boerma M ，Allen AR ... -  《-》

Late effects of (1)H irradiation on hippocampal physiology.

NASA's Missions to Mars and beyond will expose flight crews to potentially dangerous levels of charged-particle radiation. Of all charged nuclei, 1H is the most abundant charged particle in both the galactic cosmic ray (GCR) and solar particle event (SPE) spectra. There are currently no functional spacecraft shielding materials that are able to mitigate the charged-particle radiation encountered in space. Recent studies have demonstrated cognitive injuries due to high-dose 1H exposures in rodents. Our study investigated the effects of 1H irradiation on neuronal morphology in the hippocampus of adult male mice. 6-month-old mice received whole-body exposure to 1H at 0.5 and 1 Gy (150 MeV/n; 0.35-0.55 Gy/min) at NASA's Space Radiation Laboratory in Upton, NY. At 9-months post-irradiation, we tested each animal's open-field exploratory performance. After sacrifice, we dissected the brains along the midsagittal plane, and then either fixed or dissected further and snap-froze them. Our data showed that exposure to 0.5 Gy or 1 Gy 1H significantly increased animals' anxiety behavior in open-field testing. Our micromorphometric analyses revealed significant decreases in mushroom spine density and dendrite morphology in the Dentate Gyrus, Cornu Ammonis 3 and 1 of the hippocampus, and lowered expression of synaptic markers. Our data suggest 1H radiation significantly increased exploration anxiety and modulated the dendritic spine and dendrite morphology of hippocampal neurons at a dose of 0.5 or 1 Gy.

Kiffer F ，Howe AK ，Carr H ，Wang J ，Alexander T ，Anderson JE ，Groves T ，Seawright JW ，Sridharan V ，Carter G ，Boerma M ，Allen AR ... -  《-》

Effects of (1)H + (16)O Charged Particle Irradiation on Short-Term Memory and Hippocampal Physiology in a Murine Model.

Kiffer F ，Carr H ，Groves T ，Anderson JE ，Alexander T ，Wang J ，Seawright JW ，Sridharan V ，Carter G ，Boerma M ，Allen AR ... -  《-》