Getting Under Your Skin (and into your Brain): The Problematic Effects of Galactic Cosmic Radiation on Collaboration and Cognition for Long Distance Space Missions

# 3119 I am woman, watch me soar: females protected from cosmic ray-induced behavioral deficits, microglia activation and synaptic loss

Female mice are protected from space radiation-induced maladaptive responses

The Effects of Cosmic Radiation Exposure on Pregnancy During a Probable Manned Mission to Mars

Cosmic Radiation and Aircrew Exposure: Implementation of European Requirements in Civil Aviation, Dublin, 1-3 July 1998

Most terrestrial tardigrade species possess the ability to enter a reversible ametabolic state termed anhydrobiosis in response to desiccation. In theanhydrobiotic state, tardigrades display an incredible capacity to tolerate extreme environmental stress, not necessarily encountered in theirnatural habitat. In this study, we determine the effect of different extreme stresses on initial survival, long-term survival and fecundity of selectedspecies of limno-terrestrial tardigrades. The primary focus was to assess the effect of cosmic radiation. This was achieved through the RoTaRad(Rotifers, Tardigrades and Radiation) project on the BIOPAN 6 mission, funded by Agenzia Spaziale Italiana under the European Space Agency.To test their tolerance of space environment, tardigrades were sent into low earth orbit, and exposed to cosmic radiation and a microgravityenvironment. Experiments on Whatman-3 filters show an effect of cosmic radiation on the survival of the eutardigrade Richtersius coronifer justafter returning to Earth; however, after 2 years of desiccation on Whatman-3 filters, none of the tardigrades previously exposed to cosmicradiation could be revived. In a microcosmos experiment, the tardigrades R. coronifer, Ramazzottius oberhauseri and Echiniscus testudo weredesiccated on a moss substrate together with rotifers and nematodes. Very low survival rates were observed in this experiment, likely due to theapplied desiccation protocol. Embryos of the tardigrade Milnesium tardigradum were also exposed to cosmic radiation; they all hatched in thelaboratory after the flight. In addition, experiments testing extreme cold and vacuum tolerance in R. coronifer show that tardigrades inanhydrobiosis are unaffected by these conditions.Key words: Tardigrada – anhydrobiosis – cosmic radiation – extreme freezing – vacuum

To explore associations between the physical, cognitive, and mental post-intensive care syndrome (PICS) health domains with changes in health-related quality of life (HRQoL) following ICU admission. A longitudinal prospective multicenter cohort study. Patients ( n = 4092) from seven Dutch ICUs. None. At ICU admission, 3 and 12 months post-ICU, patients completed validated questionnaires regarding physical health problems, cognitive health problems, mental health problems, and HRQoL. Composite scores were created for the physical health domain (physical problems and fatigue) and mental health domain (anxiety, depression, and post-traumatic stress disorder). Adjusted multivariable linear regression analyses were performed, including covariables (e.g., patient characteristics, disease severity, pre-ICU HRQoL, etc.) to explore associations between the physical, cognitive, and mental health domains of PICS and changes in HRQoL at 3 and 12 months post-ICU. At 3 months ( n = 3368), physical health problems (β = -0.04 [95% CI, -0.06 to 0.02]; p < 0.001), cognitive health problems (β = -0.05 [95% CI, -0.09 to -0.02]; p < 0.001), and mental health problems (β = -0.08 [95% CI, -0.10 to -0.05]; p < 0.001) were negatively associated with changes in HRQoL. Also, at 12 months ( n = 2950), physical health problems (β = -0.06 [95% CI, -0.08 to -0.03]; p < 0.001), cognitive health problems (β = -0.04 [95% CI, -0.08 to -0.01]; p < 0.015), and mental health problems (β = -0.06 [95% CI, -0.08 to -0.03]; p < 0.001) were negatively associated with changes in HRQoL. PICS symptoms in the physical, cognitive, and mental domains are all negatively associated with changes in HRQoL at 3 and 12 months post-ICU. At 3 months, PICS symptoms in the mental domain seem to have the largest negative associations. At 12 months, the associations of PICS in the mental and physical domains are the same. This implies that daily ICU care and follow-up care should focus on preventing and mitigating health problems across all three PICS domains to prevent a decrease in HRQoL.

A latent class analysis of heavy substance use in Young adulthood and impacts on physical, cognitive, and mental health outcomes in middle age

Galactic cosmic radiation (GCR) exposure is increased to space flight crews as travel moves beyond low Earth orbit. GCR includes high energy protons and heavy ionizing ions such as 56Fe, 28Si, and 16O and there are distinct differences in the biological response compared to low‐energy transfer events (x‐rays). Although the exposure rate is relatively low, the cumulative radiation dose is likely to have deleterious effects for long duration flight crews. The underlying mechanisms for these elevated risks are thought to include direct DNA damage as well as chronically elevated oxidant stress, and inflammation.Given the relatively low fluence rate of GCR exposure during flight operations it might be possible to manage these deleterious effects using small molecules currently available. To that end we have utilized a FDA approved drug library to perform a high throughput screen of cultured cells following exposure to GCR. H9c2 cells were exposed to a single 75 cGy dose using the 5‐ion GCRsim protocol developed by NSRL. Following GCRsim exposure, cells were treated using 10 µM for each drug. At harvest, cells were tested for protein content, oxidant stress, cellular senescence, and mitochondrial function.Of 725 drugs, more than 500 were ineffective in managing GCR exposure. Within the top 160 drugs, 33 were primarily designated as anti‐inflammatory. Significant variations within drug classes were observed. Only 10 of 46 drugs that interacted with histamine receptors were found useful and most were 5‐HT3 specific. The COX inhibitors deemed useful were all COX2 specific. Surprisingly, some anti‐diabetic medications observed to be useful including metformin.The bias of mitochondrial degradation as a central readout comes from several “omics” analyses that identified mitochondrial dysfunction as a consequence of GCR exposure. Mitochondrial dysfunction is also an antecedent event in the transformation leading to carcinogenesis. And the potential for carcinogenesis is a significant risk for long duration space missions. Separate from examining mitochondrial and cellular dysfunction as readouts, we have developed a Afp‐tdTomato expressing cell line that is responsive to different carcinogenic reagents including GCR. We have observed that some of the lead candidates will at least partially rescue the cells from GCR induced Afp driven expression. Additionally adapting cell doubling time protocols we observed that GCR exposure significantly increased cell doubling time; a finding indicative of mitotic dysfunction. We also observed that this increase was partially ameliorated by some of the lead candidates. That no one class of drug dominated the response to radiation exposure speaks to the complexity of managing GCR exposure.

The effect of cosmic radiation on astronauts is a major barrier for human space exploration. In particular, medical protection against heavy ion radiation-induced injury is one of the key approaches in counteracting cosmic radiation to humans. In recent years, with the rapid accumulation of high-throughput data including gene expression profiles and omics-based data such as protein-protein interactions (PPI), large-scaled network pharmacology analyses can now be conducted. Exploring human genes with potentially high correlation to protection against radiation is becoming an important component and a new approach in heavy ion radiation study owing to advances in rational computational methods based on systems biology techniques. In this study, heavy ion accelerators were employed to simulate cosmic radiation and a pipeline was constructed to identify activated subnetworks of significantly differentially expressed genes and to predict essential genes related to radiation-induced injury protection. Human lymphoblastoid AHH-1 cells were irradiated with 0.5 or 2 Gy of carbon ions (12C6+). Two kinds of existing radioprotective agents 523 and VND3207 were separately used in vitro 0.5 h before irradiation. Gene expression profiles of the cells were obtained by microarray 4 h after irradiation without and with the treatment of radioprotective agents. The networks of gene expression regulation were constructed based on PPI integrated from Human Protein Reference Database (HPRD). Simulated annealing algorithm was then used to extract activated subnetworks and potential candidate molecular targets including PPM1A , RIF1 , CASP3 , TFE3 and RIN1 were proposed according to their degrees of connection. Further gene set enrichment analysis (GSEA) indicated significantly enriched clusters of the identified genes in molecular functions including transcription regulator activity, transcription activator activity, enzyme activator activity, protein kinase activity and zinc ion binding. The most enriched clusters in cell components included nuclear body, transcription factor complex, cell junction, chromosome and cytoplasmic side of membrane. The most enriched biological processes were regulation of RNA metabolism, intracellular signal transduction, regulation of neuron death, regulation of cellular component and phosphorylation. We further investigated the expression of RIF1 before and after irradiation with 0.5 and 2 Gy of 12C6+ in Hela cells by western blotting. Expression of RIF1 increased significantly after irradiation and the relative expression in cells 4h after irradiation was greater than 2-fold that of the control. This study took gene correlation into consideration in addition to their differential expression. It provides promising candidates for further discovery of anti-radiation drugs and will be of importance in promoting cosmic radiation protection techniques in long-term manned space programs and deep space exploration missions. In addition, considerable support and clues may also be revealed from the data generated in this study for future research on the underlying mechanisms in radiation-induced injury and medical protection against cosmic radiation.

Different countermeasures against deleterious effects of space radiation on human health are required for galactic cosmic rays (GCR) and solar particle events (SPE). In case of SPE, efficient shielding is possible in a radiation shelter. The crew has to enter the shelter in case of increasing proton fluxes during an SPE to avoid high-dose exposures within hours or days which might lead to the acute radiation syndrome (ARS) in worst case scenarios. ARS treatment strategies are available but difficult to implement on a space mission. The chronic exposure to GCR is associated with various health risks (cancer, cataract, CNS decrements, cardiovascular disease) that can reduce the healthy life span after return to Earth. Shielding of GCR in free space is very limited and therefore, the time in free space should be minimized by fast propulsion. On planetary and moon surfaces, the habitats should provide optimal shielding in order to reduce GCR dose accumulated during the mission. Much effort is placed on the development of nutritional and pharmaceutical countermeasures for chronic and late radiation effects. Free radical scavengers such as amifostine are ruled out because of severe side effects. Encouraging results were reported in rodent studies with berries or dried plums. A concerted action of ground-based studies and space experiments is required to expand radiobiological knowledge about space radiation to improve countermeasure development. Crew selection is a sensitive topic, but from a radiation protection point of view, the lower radiosensitivity of older crew members might be considered.

There appears to be concern among some people about the possible effects of cosmic radiation on everyday life. The amount of cosmic radiation that reaches the Earth and its environment is a function of solar cycle, altitude and latitude. The possible effect of naturally occurring cosmic radiation on airplane crews and space flight personal is a subject of current study. This paper discusses the variables controlling the cosmic ray flux in the atmosphere and describes models and software that have been developed that provide quantitative information about the cosmic radiation exposure at flight altitudes. The discussion is extended to include the cosmic radiation exposure to manned spacecraft.KeywordsSolar CycleNeutron MonitorCosmic RadiationSolar Energetic Particle EventSolar Proton EventThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

To report the ophthalmological risks of space travel. The literature about the effect of microgravity and cosmic radiation on the human eye has been reviewed, focusing on the so-called "spaceflight related neuro-ocular syndrome (SANS)", and possible remedies. The eye is the major candidate to suffer from the adverse space conditions, so much so that SANS is the main concern of the National Aeronautics and Space Administration (NASA). SANS, that affects astronauts engaged in long-duration spaceflights, is characterized by optic nerve head swelling, flattening of the posterior region of the scleral shell, choroidal folds, retinal cotton wool spots, and hyperopic shift. Even if it seems related to an increased volume of the cerebrospinal fluid in the brain and the optic nerve sheaths, its pathogenesis is still unclear. In addition, cataract is related to the effect of galactic cosmic rays on the lens. Centrifuges, pressurizing chambers, and mechanical counter-pressure suits have been advanced to counteract the upward fluid shift responsible for the SANS syndrome. Shields with a high content of hydrogen, magnetic shielding systems, and wearable radiation shielding devices are under study to mitigate the exposure to galactic cosmic rays. Since 1961, the year of the first manned mission outside the Earth, history has shown that the human being may venture in space. Yet, visual impairment is the top health risk for long-duration spaceflight. Effective remediation is mandatory in anticipation of long space missions and Moon and Mars colonization.

With the rapid development of human space explorations, whether human embryos can develop normally and reproduce beyond the planet of Earth has become a topic of concern for the scientific community and the general public. The long-term exposure to the space environmental factors poses potential hazards to embryonic development and reproductive health of mammals, and they are linked to the adverse effects of microgravity and cosmic radiation. In this review, we summarized the progress in the studies of the reproduction and development of mammals performed in spacecrafts, and with ground-based simulated microgravity and radiation by us and other groups. In particular, we discussed the study of the development of mouse preimplantation embryos under space conditions using the SJ-10 recoverable satellite which was recently published in National Science Review . The potential future studies of mammalian reproductive function and embryonic development in the space environment have also been briefly discussed and proposed. In summary, to accomplish human breeding in the outer space when other planets are colonized, further systematic evaluation of the effects of microgravity, cosmic radiation or other cosmic factors on reproductive and ontogenetic processes is required, while the protective methodology for reducing the reproductive hazards during spaceflight is also needed.

Human exploration of the solar system will expose crew members to galactic cosmic radiation (GCR), with a potential for adverse health effects. GCR particles (protons and ions) move at nearly the speed of light and easily penetrate space station walls, as well as the human body. Previously, we have shown reactivation of latent herpesviruses, including herpes simplex virus, Varicella zoster virus, Epstein-Barr virus, and cytomegalovirus (CMV), during stays at the International Space Station. Given the prevalence of latent CMV and the known propensity of space radiation to cause alterations in many cellular processes, we undertook this study to understand the role of GCR in reactivating latent CMV. Latently infected Kasumi cells with CMV were irradiated with 137Cs gamma rays, 150 MeV protons, 600 MeV/n carbon ions, 600 MeV/n iron ions, proton ions, and simulated GCR. The CMV copy number increased significantly in the cells exposed to radiation as compared with the non-irradiated controls. Viral genome sequencing did not reveal significant nucleotide differences among the compared groups. However, transcriptome analysis showed the upregulation of transcription of the UL49 ORF, implicating it in the switch from latent to lytic replication. These findings support our hypothesis that GCR may be a strong contributor to the reactivation of CMV infection seen in ISS crew members.

Enhanced GEANT4 Monte Carlo simulations of the space radiation effects on the International Space Station and Apollo missions using high-performance computing environment