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Latent Herpes Viruses Reactivation in Astronauts

Space flight has many adverse effects on human physiology. Changes in multiple systems, including the cardiovascular, musculoskeletal, neurovestibular, endocrine, and immune systems have occurred (12, 32, 38, 39). Alterations in drug pharmacokinetics and pharmacodynamics (12), nutritional needs (31), renal stone formation (40), and microbial flora (2) have also been reported. Evidence suggests that the magnitude of some changes may increase with time in space. A variety of changes in immunity have been reported during both short (.16 days) and long (>30 days) space missions. However, it is difficult to determine the medical significance of these immunological changes in astronauts. Astronauts are in excellent health and in superb physical condition. Illnesses in astronauts during space flight are not common, are generally mild, and rarely affect mission objectives. In an attempt to clarify this issue, we identified the latent herpes viruses as medically important indicators of the effects of space flight on immunity. This chapter demonstrates that space flight leads to asymptomatic reactivation of latent herpes viruses, and proposes that this results from marked changes in neuroendocrine function and immunity caused by the inherent stressfullness of human space flight. Astronauts experience uniquely stressful environments during space flight. Potential stressors include confinement in an unfamiliar, crowded environment, isolation, separation from family, anxiety, fear, sleep deprivation, psychosocial issues, physical exertion, noise, variable acceleration forces, increased radiation, and others. Many of these are intermittent and variable in duration and intensity, but variable gravity forces (including transitions from launch acceleration to microgravity and from microgravity to planetary gravity) and variable radiation levels are part of each mission and contribute to a stressful environment that cannot be duplicated on Earth. Radiation outside the Earth's magnetosphere is particularly worrisome because it includes ionizing radiation from cosmic galactic radiation. Increased stress levels appear even before flight, presumably from the rigors of preflight training and the anticipation of the mission (12, 32, 38, 39). Space flight causes significant changes in human immune function (32), but the means by which these changes come about have been difficult to discern. Consistent indicators of stress associated with space flight include increased production of stress hormones, and changes in cells of the immune system. These changes include elevated white blood cell (WBC) and neutrophil counts at landing (15, 16, 35, 37). Activation of generalized stress responses before, during, and after space flight probably affects the function of the immune system. Space flight has been shown to decrease many aspects of immune function, including natural killer (NK) cell activity, interferon production, the blastogenic response of leukocytes to mitogens, cell-mediated immunity, neutrophil function and monocyte function (5, 16, 18, 21, 35-37).

Mehta, Satish K.↗

Latent Virus Reactivation in Astronauts and Shingles Patients

Spaceflight is a uniquely stressful environment with astronauts experiencing a variety of stressors including: isolation and confinement, psychosocial, noise, sleep deprivation, anxiety, variable gravitational forces, and increased radiation. These stressors are manifested through the HPA and SAM axes resulting in increased stress hormones. Diminished T-lymphocyte functions lead to reactivation of latent herpesviruses in astronauts during spaceflight. Herpes simplex virus reactivated with symptoms during spaceflight whereas Epstein-Barr virus (EBV), cytomegalovirus (CMV), and varicella zoster virus (VZV) reactivate and are shed without symptoms. EBV and VZV are shed in saliva and CMV in the urine. The levels of EBV shed in astronauts increased 10-fold during the flight; CMV and VZV are not typically shed in low stressed individuals, but both were shed in astronauts during spaceflight. All herpes viruses were detected by polymerase chain reaction (PCR) assay. Culturing revealed that VZV shed in saliva was infectious virus. The PCR technology was extended to test saliva of 54 shingles patients. All shingles patients shed VZV in their saliva, and the levels followed the course of the disease. Viremia was also found to be common during shingles. The technology may be used before zoster lesions appear allowing for prevention of disease. The technology may be used for rapid detection of VZV in doctors offices. These studies demonstrated the value of applying technologies designed for astronauts to people on Earth.

Mehta, Satish K.↗

Salivary Varicella Zoster Virus in Astronauts and in Patients of Herpes Zoster

Spaceflight is a uniquely stressful environment with astronauts experiencing a variety of stressors including: isolation and confinement, psychosocial, noise, sleep deprivation, anxiety, variable gravitational forces, and increased radiation. These stressors are manifested through the HPA and SAM axes resulting in increased stress hormones. Diminished T-lymphocyte functions lead to reactivation of latent herpes viruses in astronauts during spaceflight. Herpes simplex virus reactivated with symptoms during spaceflight whereas Epstein-Barr virus (EBV), cytomegalovirus (CMV), and varicella zoster virus (VZV) reactivate and are shed without symptoms. EBV and VZV are shed in saliva and CMV in the urine. The levels of EBV shed in astronauts increased 10-fold during the flight; CMV and VZV are not typically shed in low stressed individuals, but both were shed in astronauts during spaceflight. All herpesviruses were detected by polymerase chain reaction (PCR) assay. Culturing revealed that VZV shed in saliva was infectious virus. The PCR technology was extended to test saliva of 54 shingles patients. All shingles patients shed VZV in their saliva, and the levels followed the course of the disease. Viremia was also found to be common during shingles. The technology may be used before zoster lesions appear allowing for prevention of disease. The technology may be used for rapid detection of VZV in doctors? offices. These studies demonstrated the value of applying technologies designed for astronauts to people on Earth.

Mehta, Satish↗

Effects of Unpredictable Variable Prenatal Stress (UVPS) on Bdnf DNA Methylation and Telomere Length in the Adult Rat Brain

In utero exposure to stress can shape neurobiological and behavioral outcomes in offspring, producing vulnerability to psychopathology later in life. Animal models of prenatal stress likewise have demonstrated long-­‐term alterations in brain function and behavioral deficits in offspring. For example, using a rodent model of unpredictable variable prenatal stress (UVPS), in which dams are exposed to unpredictable, variable stress across pregnancy, we have found increased body weight and anxiety-­‐like behavior in adult male, but not female, offspring. DNA methylation (addition of methyl groups to cytosines which normally represses gene transcription) and changes in telomere length (TTAGGG repeats on the ends of chromosomes) are two molecular modifications that result from stress and could be responsible for the long-­‐term effects of UVPS. Here, we measured methylation of brain-­‐derived neurotrophic factor (bdnf), a gene important in development and plasticity, and telomere length in the brains of adult offspring from the UVPS model. Results indicate that prenatally stressed adult males have greater methylation in the medial prefrontal cortex (mPFC) compared to non-­‐stressed controls, while females have greater methylation in the ventral hippocampus compared to controls. Further, prenatally stressed males had shorter telomeres than controls in the mPFC. These findings demonstrate the ability of UVPS to produce epigenetic alterations and changes in telomere length across behaviorally-­‐relevant brain regions, which may have linkages to the phenotypic outcomes.

epigenetic developmental programming↗

Self-Guided Multimedia Stress Management and Resilience Training for Flight Controllers

Stress and anxiety-related problems are among the most common and costly behavioral health problems in society, and for those working in operational environments (i.e. astronauts, flight controllers, military) this can seriously impact crew performance, safety, and wellbeing. Technology-based interventions are effective for treating behavioral health problems, and can significantly improve the delivery of evidence-based health care. This study is evaluating the effectiveness, usefulness, and usability of a self-guided multimedia stress management and resilience training program in a randomized controlled trial (RCT) with a sample of flight controllers at Johnson Space Center. The intervention, SMART-OP (Stress Management and Resilience Training for Optimal Performance), is a six-session, cognitive behavioral-based computer program that uses self-guided, interactive activities to teach skills that can help individuals build resilience and manage stress. In a prior RCT with a sample of stressed but otherwise healthy individuals, SMART-OP reduced perceived stress and increased perceived control over stress in comparison to an Attention Control (AC) group. SMART-OP was rated as "highly useful" and "excellent" in usability and acceptability. Based on α-amylase data, individuals in SMART-OP recovered quicker and more completely from a social stress test as compared to the AC group [1]. In the current study, flight controllers are randomized either to receive SMART-OP training, or to a 6-week waitlist control period (WLC) before beginning SMART-OP. Eligible participants include JSC flight controllers and instructors without any medical or psychiatric disorder, but who are stressed based on self-report. Flight controllers provide a valid analog sample to astronauts in that they work in an operational setting, use similar terminology to astronauts, are mission-focused, and work under the same broader work culture. The study began in December 2014, and to date 79 flight controllers and instructors have expressed interest in the study, 49 of those were cleared for participation, we have screened 44 for eligibility, and 23 have met inclusion criteria. Recruitment is ongoing and the study will continue until December 2016. Outcome measures include perceived stress, perceived control over stress, resilience, mood, personality, emotion regulation, sleep, health behaviors, and psychophysiological data such as 24-hour heart rate, alpha amylase, and urinary and salivary cortisol. We are also collecting user feedback such as usability, working alliance, usefulness, and treatment credibility.

Rose, R. D.↗

Risk of Adverse Cognitive or Behavioral Conditions and Psychiatric Disorders: Evidence Report

In April 2010, President Obama declared a space pioneering goal for the United States in general and NASA in particular. "Fifty years after the creation of NASA, our goal is no longer just a destination to reach. Our goal is the capacity for people to work and learn and operate and live safely beyond the Earth for extended periods of time, ultimately in ways that are more sustainable and even indefinite." Thus NASA's Strategic Objective 1.1 emerged as "expand human presence into the solar system and to the surface of Mars to advance exploration, science, innovation, benefits to humanity, and international collaboration" (NASA 2015b). Any space flight, be it of long or short duration, occurs in an extreme environment that has unique stressors. Even with excellent selection methods, the potential for behavioral problems among space flight crews remain a threat to mission success. Assessment of factors that are related to behavioral health can help minimize the chances of distress and, thus, reduce the likelihood of adverse cognitive or behavioral conditions and psychiatric disorders arising within a crew. Similarly, countermeasures that focus on prevention and treatment can mitigate the cognitive or behavioral conditions that, should they arise, would impact mission success. Given the general consensus that longer duration, isolation, and confined missions have a greater risk for behavioral health ensuring crew behavioral health over the long term is essential. Risk, which within the context of this report is assessed with respect to behavioral health and performance, is addressed to deter development of cognitive and behavioral degradations or psychiatric conditions in space flight and analog populations, and to monitor, detect, and treat early risk factors, predictors and other contributing factors. Based on space flight and analog evidence, the average incidence rate of an adverse behavioral health event occurring during a space mission is relatively low for the current conditions. While mood and anxiety disturbances have occurred, no behavioral emergencies have been reported to date in space flight. Anecdotal and empirical evidence indicate that the likelihood of an adverse cognitive or behavioral condition or psychiatric disorder occurring greatly increases with the length of a mission. Further, while cognitive, behavioral, or psychiatric conditions might not immediately and directly threaten mission success, such conditions can, and do, adversely impact individual and crew health, welfare, and performance.

Slack, Kelley J.↗

Behavioral Adaptations of Female Mice on the International Space Station

Adult female mice were sent to the International Space Station (ISS) as part of an early life science mission utilizing NASA's Rodent Habitat. Its primary purpose was to provide further insight into the influence of a microgravity environment on various aspects of mammalian physiology and well-being as part of an ongoing program of research aimed ultimately at understanding and ameliorating the deleterious influences of space on the human body. The present study took advantage of video collected from fixed, in-flight cameras within the habitat itself, to assess behavioral adaptations observed among in-flight mice aboard the ISS and differences in behavior with respect to a control group on the ground. Data collection consisted of several behavioral measures recorded by a trained observer with the assistance of interactive behavior analysis software. Specific behavioral measures included frequencies of conspecific interactionsociability, time spent feeding and conducting hygienic behavior, and relative durations of thigmotactic behavior, which is commonly used as an index of anxiety. Data were used to test tentative hypotheses that such behaviors differ significantly across mice under microgravity versus 1g conditions, and the assumption that the novel experience of microgravity itself may represent an initially anxiogenic stimulus which an animal will eventually acclimate to, perhaps through habituation.

Behavior in space↗

Developmental Research in Space: Predicting Adult Neurobehavioral Phenotypes via Metabolomic Imaging

As human habitation and eventual colonization of space becomes an inevitable reality, there is a necessity to understand how organisms develop over the life span in the space environment. Microgravity, altered CO2, radiation and psychological stress are some of the key factors that could affect mammalian reproduction and development in space, however there is a paucity of information on this topic. Here we combine early (neonatal) in vivo spectroscopic imaging with an adult emotionality assay following a common obstetric complication (prenatal asphyxia) likely to occur during gestation in space. The neural metabolome is sensitive to alteration by degenerative changes and developmental disorders, thus we hypothesized that that early neonatal neurometabolite profiles can predict adult response to novelty. Late gestation fetal rats were exposed to moderate asphyxia by occluding the blood supply feeding one of the rats pair uterine horns for 15min. Blood supply to the opposite horn was not occluded (within-litter cesarean control). Further comparisons were made with vaginal (natural) birth controls. In one-week old neonates, we measured neurometabolites in three brain areas (i.e., striatum, prefrontal cortex, and hippocampus). Adult perinatally-asphyxiated offspring exhibited greater anxiety-like behavioral phenotypes (as measured the composite neurobehavioral assay involving open field activity, responses to novel object, quantification of fecal droppings, and resident-intruder tests of social behavior). Further, early neurometabolite profiles predicted adult responses. Non-invasive MRS screening of mammalian offspring is likely to advance ground-based space analogue studies informing mammalian reproduction in space, and achieving high-priority multigenerational research that will enable studies of the first truly space-developed mammals.

Schorn, Julia M.↗

Behavioral Adaptations of Female Mice on the International Space Station

Adult female mice were sent to the International Space Station (ISS) as part of an early life science mission utilizing NASA's Rodent Habitat. Its primary purpose was to provide further insight into the influence of a microgravity environment on various aspects of mammalian physiology and well-being as part of an ongoing program of research aimed ultimately at understanding and ameliorating the deleterious influences of space on the human body. The present study took advantage of video collected from fixed, in-flight cameras within the habitat itself, to assess behavioral adaptations observed among in-flight mice aboard the ISS and differences in behavior with respect to a control group on the ground. Data collection consisted of several behavioral measures recorded by a trained observer with the assistance of interactive behavior analysis software. Specific behavioral measures included frequencies of conspecific interactionsociability, time spent feeding and conducting hygienic behavior, and relative durations of thigmotactic behavior, which is commonly used as an index of anxiety. Data were used to test tentative hypotheses that such behaviors differ significantly across mice under microgravity versus 1g conditions, and the assumption that the novel experience of microgravity itself may represent an initially anxiogenic stimulus which an animal will eventually acclimate to, perhaps through habituation.

rodent behavior↗

Developmental Research in Space: Predicting Adult Neurobehavioral Phenotypes via Metabolomic Imaging

As human habitation and eventual colonization of space becomes an inevitable reality, there is a necessity to understand how organisms develop over the life span in the space environment. Microgravity, altered CO2, radiation and psychological stress are some of the key factors that could affect mammalian reproduction and development in space, however there is a paucity of information on this topic. Here we combine early (neonatal) in vivo spectroscopic imaging with an adult emotionality assay following a common obstetric complication (prenatal asphyxia) likely to occur during gestation in space. The neural metabolome is sensitive to alteration by degenerative changes and developmental disorders, thus we hypothesized that that early neonatal neurometabolite profiles can predict adult response to novelty. Late gestation fetal rats were exposed to moderate asphyxia by occluding the blood supply feeding one of the rats pair uterine horns for 15min. Blood supply to the opposite horn was not occluded (within-litter cesarean control). Further comparisons were made with vaginal (natural) birth controls. In one-week old neonates, we measured neurometabolites in three brain areas (i.e., striatum, prefrontal cortex, and hippocampus). Adult perinatally-asphyxiated offspring exhibited greater anxiety-like behavioral phenotypes (as measured the composite neurobehavioral assay involving open field activity, responses to novel object, quantification of fecal droppings, and resident-intruder tests of social behavior). Further, early neurometabolite profiles predicted adult responses. Non-invasive MRS screening of mammalian offspring is likely to advance ground-based space analogue studies informing mammalian reproduction in space, and achieving high-priority.

rodent development spacefligh↗

Effects of Acute Stress on Aircrew Performance: Literature Review and Analysis of Operational Aspects

Situational stress can adversely affect the cognition and skilled performance of pilots, as well as experts in other domains. Emergencies and other threatening situations require pilots to execute infrequently practiced procedures correctly and to use their skills and judgment to select an appropriate course of action, often under high workload, time pressure, and ambiguous indications, all of which can be stressful. Our current study, consited of three parts, starting with a critical review of the research literature on the effects of stress on skilled performance, going back to World War II and continuing to recent and more sophisticated studies of the cognitive effects of anxiety. In the second part we analyzed the specific ways stress may have impaired the performance of airline crews in twelve major accidents, selected for diversity of the situations the crews encountered. The third part examined the operational significance and practical implications of the findings from the first two parts, suggested specific ways to reduce the harmful effects of stress on flight crews, and identified aspects requiring further research. Even thought this study focused on flight crews, the findings apply to the effects of stress on the skilled performance of experts in almost any domain.

stress↗

Prenatal 2g Exposure Alters Placental Expression of Stress-Related Genes

Extra-terrestrial colonization is of growing interest to space agencies and private entities, emphasizing the importance of research on reproduction and development in the absence of Earth's 1G. Maternal stressors can modify offspring development, exerting significant lifespan and crossgenerational changes through prenatal programming. The space environment is stressful, therefore exposure to altered gravity during pregnancy may impact later life outcomes in offspring. In ground-based studies, we exposed pregnant rats to continuous +G (above Earth gravity), and observed overweight and elevated anxiety in adult male (but not female) offspring, common phenotypes associated with prenatal maternal stress. Here we hypothesize that exposure to increased gravity during pregnancy elicits changes in the expression of stress-related genes in placenta that may mediate emergence of later life outcomes. While the placenta transports maternal factors to the fetus and produces endogenous fetal hormones, stress-induced changes at the placental-uterine interface may also alter communication between mother and fetus, facilitating prenatal transmission of unfavorable later life outcomes and cross-generational epigenetic alterations. Maternal stress elevates maternal glucocorticoids however placental 11b-hydroxysteroid dehydrogenase type 2 (HSD11B2) buffers fetal exposure by converting cortisol/corticosterone into inactive metabolites. Maternal stress during pregnancy down-regulates this enzyme and can induce epigenetic changes in placental and fetal tissues accounting for heightened adult HPA reactivity. Past studies have shown a placenta-specific increase in DNA methyltransferase (DNMT3a) mRNA in stressed mothers, an effect with implications for genome-wide epigenetic changes that may account for diverse phenotypic outcomes following maternal stress. Here we exposed groups of pregnant rats to one of five gravity loads (1, 1.5, 1.75 and 2G) and analyzed placental samples during late gestation. We predicted a systematic dose-response relationship between gravity load and the expression of the HSD11B2 and DNMT3 genes, thereby linking maternal exposure to altered gravity during pregancy with maternal stress.

Kalotia, Simranjit K.↗

The Effects of Placental-expanded (PLX-PAD) Stromal Cell Treatment, Hindlimb Unloading, and Isolation on the Behavior of Female Mice

Spaceflight can lead to altered immune responses and inflammation (Crucian et al. 2014) and elevated levels of inflammation are connected to anxiety and depression. A recent study on the International Space Station showed that mice exhibited a novel circling behavior during spaceflight (Ronca et al. 2019). However, there is still a gap in knowledge on how microgravity impacts behavior. In this current study, we performed 30 days of hindlimb unloading (HU) on four-month old female mice and analyzed select behavior from video image capture. We also determined the effects of PLacental-eXpanded stromal cells derived from the maternal placenta (PLX-PAD), alone and in combination with HU and isolation, on behavior. We have previously shown that PLX-PAD mitigates select inflammatory responses and changes in cytokine expression caused by HU. In-cage behaviors were analyzed in HU or control female mice treated with 2 injections of PlasmaLyte (Sham) or PLX-PAD (n=7/group). We found that PLX-PAD decreased exploratory behaviors compared to Sham-treated mice at night. Normally loaded (NL) PLX mice slept less than NL Sham mice during the day, and HU animals had significantly higher involuntary movement during sleep compared to NL animals, suggesting sleep disruption. Overall, we show that both HU and PLX affect important behavioral factors. This experiment is the first to study the effects of PLX-PAD on behavior. Additional studies are needed to define the behavioral changes in spaceflight and test possible countermeasures.

PLacental-EXpanded stromal cells, behavior, microg↗

Behavioral consequences of low dose radiation and sex differences in MCAT mouse model

Our study used 1-year old C57BL/6NJ male and female mice (astronaut-relevant age) that underwent exposure to 0.5 gray of gamma radiation and were euthanized 12 weeks after. In this study, we used an MCAT mouse model for mitochondrial ROS quenching, which overexpress human catalase. MCAT mice were shown to live longer and age better. Hence, in this study we determined whether quenching ROS in the mitochondria will mitigate the adverse effects of ionizing radiation exposure on spaceflight-relevant tissues. As part of the analysis, we have completed 5 different behavioral tests which focus on memory, physical stance, stress, anxiety, and other mission relevant behaviors. In the Neuro-score battery, performed after both 1and 8 weeks post IR we saw that all female groups had significantly higher scores compared to males. When comparing the baseline vs 8 weeks of radiation, we saw that all the male groups (including the sham) had lower neuro-score, pointing out to aging effect in addition to IR. In the female groups only the female IR group had lower neuro-score and the MCAT group was protected from this effect. In the Nestlet building test we saw similarly that only females were affected by radiation, having lower scores and this effect was mitigated in the MCAT animals as well. In the Catwalk test we saw that females were faster, had higher swing speed and stride length in all four paws. Males had higher stand, step cycle and max contact area. Aging is associated with slowing of gait speed, swing speed and shortening of stride length which we see in males, this is consistent with physical appearance where males look markedly older. In the Light-Dark Box test we saw that females were more frequently present in the light side and altered zones more frequently, pointing out to a more exploratory and less anxious pattern of behavior. Similarly, to what was detected in the Nest building and Neuro-score test, in the Barnes maze test, during the acquisition phase (learning) we saw that IR affected more the females who did not do better in the maze after 4 days. On the other hand, during the probe phase of the test (spatial memory) the females visited the target hole and the box quadrant more often, but also had more errors vs males, which points out to possible serial escape vs spatial escape strategy. Overall, we see that older females look physically better are faster and perform better almost in all behavioral tests compared to their male counterparts. On the other hand, they are more sensitive to low dose radiation in many cases, in some cases this effect was mitigated in the MCAT model pointing out to the importance of ROS in these stressors. In the near future we will focus on corelating these behavioral tests with molecular findings such as for example brain IHC, plasma and hippocampal cytokines in order to find specific biomarkers for behavioral deficits.

radiation↗

The Effects of Simulated Microgravity and PLacental-EXpanded (PLX-PAD) Stromal Cell Treatment on The Behavior and Correlation with Cytokine Profiles in Female Mice

Spacelight can lead to altered immune responses and inflammation (Crucian et al. 2014) and elevated levels of inflammation are connected to anxiety and depression. A recent study on the International Space Station showed that mice exhibited a novel circling behavior during spaceflight (Ronca 2019). However, there is still a gap in knowledge on how microgravity impacts behavior. In this current study, we performed 30 days of hindlimb unloading (HU) on four-month old female mice and analyzed select behavior from video image capture. We also determined the effects of PLacental-eXpanded stromal cells dervided from the maternal placenta (PLX-PAD), alone and in combination with HU and isolation, on behavior. We have previoulst shown that PLX-PAD mitigated select inflammatory responses and changes in cytokine expression causes by HU. In-cage behaviors were analyzed in HU or control female mice treated with 2 injections of PlasmaLyte (Sham) or PLX-PAD (n=7/group). We found that PLX-PAD decreased exploratory behaviors compared to Sham treated mice at night. Normally loaded (NL) PLX mice slept less than NL Sham mice during the day, and HU animals had signficantly higher involuntary movement during sleep compared to NL animals, suggesting sleep distruption. Overall, we show that both HU and PLX affect important behavioral factors., This experiment is the first to study the effects of PLX-PAD on behavior. Additional studies are needed to define the behavioral changes in spaceflight and test possible countermeasures. Funding for this project was provided through the 2019 Ames Research Innovation Award (ARIA) provided by NASA Ames Research Center.

Stromal cell treatment↗

Neurobehavioral Effects Of Five-Ion GCRSim Exposure In Male And Female Mice

Exposure to space galactic cosmic radiation is a principal consideration of spaceflight missions, and with upcoming missions to the Moon and Mars, it is increasingly imperative to elucidate the detrimental effects of space travel beyond the lower Earth orbit. Additionally, with the first female astronaut to soon travel to the Moon and beyond lower Earth orbit, there is a strong need to understand the biological sex differences to adaptation to the deep space environment. While the effects of spaceflight on the nervous system are not fully known, studies in animal models have shown that exposure to ionizing radiation can cause neuronal damage and lead to downstream cognitive and behavioral deficits. Therefore, we investigated the neurobehavioral responses to space environment-like radiation exposure. Male and female 23–24-week-old mice (age-matched to average astronaut age) were exposed to 5, 15 and 50 cGy via Five-Ion Galactic Cosmic Ray Simulation at the NASA National Space Radiation Laboratory at Brookhaven National Laboratory. Both early (72hrs post exposure) and late (1-4 months post exposure) cognitive and behavioral deficits were investigated. In-cage behavior was analyzed as frequency/duration of digging, rearing, and grooming and nestlet building using a 5-stage Deacon score. Additionally, at NASA Ames, behavior tests included Catwalk (gait), Zero Maze (anxiety), Adhesive Removal (sensory motor), Novel Object Recognition and Barnes Maze (working memory). There were pronounced sex differences in both early and late time points. Females typically performed the tests better than males, specifically in nestlet building, gait and working memory, though males performed better at the sensory motor (adhesive removal) test. Dose effects were primarily observed at 50 cGy for both sexes, particularly with the Barnes Maze (working memory), where both males and females exposed to 50 cGy showed little to no improvement in test performance, though females again performed better than males. Currently, we are investigating the correlations between the observed behavior and cytokine levels in the plasma and brain. Future studies will continue to investigate cognitive consequences of galactic cosmic radiation in combination with other space-like environment stressors, including antigravity and social versus single housing.

Stephanie Puukila↗

Early And Late Neurobehavioral Effects Of Male And Female Mice Exposed To Five-Ion GCRSim

With upcoming missions to the Moon and beyond to Mars, it is increasingly imperative to elucidate the detrimental effects of space travel beyond the lower Earth orbit, particularly to galactic cosmic radiation. Additionally, with the first female astronaut to soon travel to the Moon there is a strong need to understand the biological sex differences to adaptation to the deep space environment. While the effects of spaceflight on the nervous system are not fully known, studies in animal models have shown that exposure to ionizing radiation can cause neuronal damage and lead to downstream cognitive and behavioral deficits. Here, we investigated the neurobehavioral responses to space environment-like radiation exposure. Male and female 23–24-week-old mice (age-matched to average astronaut age) were exposed to 5, 15 and 50 cGy via Five-Ion Galactic Cosmic Ray Simulation at the NASA National Space Radiation Laboratory at Brookhaven National Laboratory. Both early (72hrs post exposure) and late (1-4 months post exposure) cognitive and behavioral deficits were investigated. Early analysis was performed by observing in-cage behavior including frequency/duration of digging, rearing, and grooming and nestlet building. Additionally, late effects were analyzed at NASA Ames via in-cage behavior as well as Catwalk (gait), Zero Maze (anxiety), Adhesive Removal (sensory motor), Novel Object Recognition and Barnes Maze (working memory). There were pronounced sex differences in both early and late time points. Females scored better than males in nestlet building, gait and working memory while males scored better at the sensory motor (adhesive removal) test. Dose effects were primarily observed at 50 cGy for both sexes, particularly with the Barnes Maze (working memory), where both males and females exposed to 50 cGy showed little to no improvement in test performance, though females again performed better than males. Currently, we are investigating the correlations between the observed behavior and cytokine levels in the plasma and brain. Future studies will continue to investigate cognitive consequences of galactic cosmic radiation in combination with other space-like environment stressors, including antigravity and social versus single housing.

S Puukila↗

Neurobehavioral Effects Of Five-Ion GCRSim Exposure In Male And Female Mice

Exposure to space galactic cosmic radiation is a principal consideration of spaceflight missions, and with upcoming missions to the Moon and Mars, it is increasingly imperative to elucidate the detrimental effects of space travel beyond the lower Earth orbit. Additionally, with the first female astronaut to soon travel to the Moon and beyond lower Earth orbit, there is a strong need to understand the biological sex differences to adaptation to the deep space environment. While the effects of spaceflight on the nervous system are not fully known, studies in animal models have shown that exposure to ionizing radiation can cause neuronal damage and lead to downstream cognitive and behavioral deficits. Therefore, we investigated the neurobehavioral responses to space environment-like radiation exposure. Male and female 23–24-week-old mice (age-matched to average astronaut age) were exposed to 5, 15 and 50 cGy via Five-Ion Galactic Cosmic Ray Simulation at the NASA National Space Radiation Laboratory at Brookhaven National Laboratory. Both early (72hrs post exposure) and late (1-4 months post exposure) cognitive and behavioral deficits were investigated. In-cage behavior was analyzed as frequency/duration of digging, rearing, and grooming and nestlet building using a 5-stage Deacon score. Additionally, at NASA Ames, behavior tests included Catwalk (gait), Zero Maze (anxiety), Adhesive Removal (sensory motor), Novel Object Recognition and Barnes Maze (working memory). There were pronounced sex differences in both early and late time points. Females typically performed the tests better than males, specifically in nestlet building, gait and working memory, though males performed better at the sensory motor (adhesive removal) test. Dose effects were primarily observed at 50 cGy for both sexes, particularly with the Barnes Maze (working memory), where both males and females exposed to 50 cGy showed little to no improvement in test performance, though females again performed better than males. Currently, we are investigating the correlations between the observed behavior and cytokine levels in the plasma and brain. Future studies will continue to investigate cognitive consequences of galactic cosmic radiation in combination with other space-like environment stressors, including antigravity and social versus single housing.

S. Puukila↗