Galactic cosmic radiation exposure causes multifaceted neurocognitive impairments.

Technological advancements have facilitated the implementation of realistic, terrestrial-based complex 33-beam galactic cosmic radiation simulations (GCR Sim) to now probe central nervous system functionality. This work expands considerably on prior, simplified GCR simulations, yielding new insights into responses of male and female mice exposed to 40-50 cGy acute or chronic radiations relevant to deep space travel. Results of the object in updated location task suggested that exposure to acute or chronic GCR Sim induced persistent impairments in hippocampus-dependent memory formation and reconsolidation in female mice that did not manifest robustly in irradiated male mice. Interestingly, irradiated male mice, but not females, were impaired in novel object recognition and chronically irradiated males exhibited increased aggressive behavior on the tube dominance test. Electrophysiology studies used to evaluate synaptic plasticity in the hippocampal CA1 region revealed significant reductions in long-term potentiation after each irradiation paradigm in both sexes. Interestingly, network-level disruptions did not translate to altered intrinsic electrophysiological properties of CA1 pyramidal cells, whereas acute exposures caused modest drops in excitatory synaptic signaling in males. Ultrastructural analyses of CA1 synapses found smaller postsynaptic densities in larger spines of chronically exposed mice compared to controls and acutely exposed mice. Myelination was also affected by GCR Sim with acutely exposed mice exhibiting an increase in the percent of myelinated axons; however, the myelin sheathes on small calibur (< 0.3 mm) and larger (> 0.5 mm) axons were thinner when compared to controls. Present findings might have been predicted based on previous studies using single and mixed beam exposures and provide further evidence that space-relevant radiation exposures disrupt critical cognitive processes and underlying neuronal network-level plasticity, albeit not to the extent that might have been previously predicted.

Chronic Low Dose Neutron Exposure Results in Altered Neurotransmission Properties of the Hippocampus-Prefrontal Cortex Axis in Both Mice and Rats.

The proposed deep space exploration to the moon and later to Mars will result in astronauts receiving significant chronic exposures to space radiation (SR). SR exposure results in multiple neurocognitive impairments. Recently, our cross-species (mouse/rat) studies reported impaired associative memory formation in both species following a chronic 6-month low dose exposure to a mixed field of neutrons (1 mGy/day for a total dose pf 18 cGy). In the present study, we report neutron exposure induced synaptic plasticity in the medial prefrontal cortex, accompanied by microglial activation and significant synaptic loss in the hippocampus. In a parallel study, neutron exposure was also found to alter fluorescence assisted single synaptosome LTP (FASS-LTP) in the hippocampus of rats, that may be related to a reduced ability to insert AMPAR into the post-synaptic membrane, which may arise from increased phosphorylation of the serine 845 residue of the GluA1 subunit. Thus, we demonstrate for the first time, that low dose chronic neutron irradiation impacts homeostatic synaptic plasticity in the hippocampal-cortical circuit in two rodent species, and that the ability to successfully encode associative recognition memory is a dynamic, multicircuit process, possibly involving compensatory changes in AMPAR density on the synaptic surface.

Chronic Exposure to High Altitude: Synaptic, Astroglial and Memory Changes.

Long-term operations carried out at high altitude (HA) by military personnel, pilots, and astronauts may trigger health complications. In particular, chronic exposure to high altitude (CEHA) has been associated with deficits in cognitive function. In this study, we found that mice exposed to chronic HA (5000 m for 12 weeks) exhibited deficits in learning and memory associated with hippocampal function and were linked with changes in the expression of synaptic proteins across various regions of the brain. Specifically, we found decreased levels of synaptophysin (SYP) (p < 0.05) and spinophilin (SPH) (p < 0.05) in the olfactory cortex, post synaptic density-95 (PSD-95) (p < 0.05), growth associated protein 43 (GAP43) (p < 0.05), glial fibrillary acidic protein (GFAP) (p < 0.05) in the cerebellum, and SYP (p < 0.05) and PSD-95 (p < 0.05) in the brainstem. Ultrastructural analyses of synaptic density and morphology in the hippocampus did not reveal any differences in CEHA mice compared to SL mice. Our data are novel and suggest that CEHA exposure leads to cognitive impairment in conjunction with neuroanatomically-based molecular changes in synaptic protein levels and astroglial cell marker in a region specific manner. We hypothesize that these new findings are part of highly complex molecular and neuroplasticity mechanisms underlying neuroadaptation response that occurs in brains when chronically exposed to HA.

Alterations in synaptic density and myelination in response to exposure to high-energy charged particles.

High-energy charged particles are considered particularly hazardous components of the space radiation environment. Such particles include fully ionized energetic nuclei of helium, silicon, and oxygen, among others. Exposure to charged particles causes reactive oxygen species production, which has been shown to result in neuronal dysfunction and myelin degeneration. Here we demonstrate that mice exposed to high-energy charged particles exhibited alterations in dendritic spine density in the hippocampus, with a significant decrease of thin spines in mice exposed to helium, oxygen, and silicon, compared to sham-irradiated controls. Electron microscopy confirmed these findings and revealed a significant decrease in overall synapse density and in nonperforated synapse density, with helium and silicon exhibiting more detrimental effects than oxygen. Degeneration of myelin was also evident in exposed mice with significant changes in the percentage of myelinated axons and g-ratios. Our data demonstrate that exposure to all types of high-energy charged particles have a detrimental effect, with helium and silicon having more synaptotoxic effects than oxygen. These results have important implications for the integrity of the central nervous system and the cognitive health of astronauts after prolonged periods of space exploration.