Galactic cosmic radiation exposure causes multifaceted neurocognitive impairments

Abstract

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.

The longitudinal behavioral effects of acute exposure to galactic cosmic radiation in female C57BL/6J mice: implications for deep space missions, female crews, and potential antioxidant countermeasures

“…Also, the lack of effect on object recognition memory in our current work is striking given that the most commonly reported behavioral deficit after whole-body charged-particle radiation is seen in novel object recognition (NOR) assessments (Cacao and Cucinotta 2019). However, prior work with female mice also shows intact NOR 3.5 mon after chronic (50cGy) or acute (40 cGy) 33-GCR; notably, male mice in that study had disrupted NOR (Alaghband et al 2023). Thus, future work should test if 33-GCR-induced deficits in NOR are indeed sex-specific.…”

“…Thus, we conclude that this dose (∼75cGy total in 1 day) of whole-body 33-GCR does not influence behavioral pattern separation assessed via LDR, at least at this time examined post-IRR. In contrast, other work shows that female C57BL/6J mice that received either acute or repeated exposure to 33-GCR (∼50 cGy total over 24 days) had worse behavioral pattern separation relative to control female mice, as assessed in the OUL (object in updated location) test (Alaghband et al . 2023); the authors state such changes did not “manifest” in the male mice.…”

“…Taken together, studies show single-ion, multi-ion, and even 33-GCR disturb a range of rodent central nervous system (CNS) functions, including memory, pattern separation, anxiety, vigilance, social novelty, and motor control (Kiffer et al 2019b;Cekanaviciute et al 2018;Clément et al 2020). However, narrowing these studies to just those that use multi-particle GCR (multi-ion, up to 33-GCR) highlights some contradictory results (Raber et al 2016;Kiffer et al 2018;Krukowski et al 2018a;Raber et al 2019;Kiffer et al 2020;Raber et al 2020;Klein et al 2021;Boutros et al 2021;Krukowski et al 2021;Raber et al 2021;Schaeffer et al 2022;Britten et al 2022;Puukila et al 2023;Alaghband et al 2023;Kiffer et al 2021). In addition, while most work has been performed in just male rodents, some of these studies show sex-specific outcomes of multi-ion whole-body exposure.…”

“…Thus, the impact of multi-ion GCR, particularly the Mars-relevant 33-GCR, on higher cognitive function in female mice warrants more research. In addition, while a few papers have now looked at the behavioral impact of 33-GCR up to 6-months (mon) post-IRR (Alaghband et al 2023;Desai et al 2023), more work is needed to assess the even longer-term impact of 33-GCR, particularly given concerns about astronaut morbidity.…”

Dosimetry of the PIM1 Pion Beam at the Paul Scherrer Institute for Radiobiological Studies of Mice

“…Animal models, subjected to charged particles ranging from protons to the heavier ionized nuclei typically found in the galactic-cosmic ray (GCR) spectrum, have revealed that such exposures lead to neurocognitive complications involving a range of associated pathologies ( 3 ). Importantly, space relevant doses ≤50 cGy of nearly any individual or combination of ions have now been found to elicit persistent neuroinflammation, degradation of mature neurons throughout the brain, and impairments in learning and memory along with a host of mood disorders ( 4 , 5 ). Even more concerning for space agencies is that most of these cosmic radiation-induced disruptions in the central nervous system (CNS) functionality do not appear to resolve with time ( 1 ), even over the course of one year following exposure ( 2 , 6 ).…”