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NASA NTRSDate not supplied

Altered Immune Differentials Between Male and Female Mice Independent of Ionizing Irradiation

As upcoming exploratory missions to the Lunar surface and Mars during the Artemis Program will send both female and male crewmembers, studies identifying sex-specific effects are necessary. It is well-documented that the immune system engages different responses between females and males following exposures to infectious challenge, tumors surveillance, and autoimmune development. Yet, the immune effects of spaceflight-like exposures between the sexes are limited. Therefore, this study sought to address the effects of spaceflight-like conditions on immune differentials in female and male mice. We hypothesized that the spaceflight factor, ionizing radiation, will have sex-specific effects on immune differentials. To test this, singly-housed, 12-month old female and male wildtype (Wt) mice were exposed to acute ionizing gamma irradiation (50 cGy), followed by retro-orbital blood collections at 7-days post-irradiation. Leukocytes were analyzed by flow cytometry characterizing, granulocytes, monocytes, lymphocytes (cytotoxic/helper T cells and B cells), neutrophils, eosinophils, and NK/NKT cells. Briefly, minimal sex-specific effects were observed across the cell types listed at this time point, including changes in granulocyte and lymphocyte populations. The results revealed females displayed elevated granulocytes and reduced lymphocytes compared to their male counterparts, independent of irradiation exposure. These results suggest female mice may be more capable to produce innate inflammatory mediators but may be adaptively immune compromised. In brief, this study provides insight into the sex-specific immune risks following ionizing radiation that may be experienced during spaceflight, which is relevant for future countermeasure development.

spaceflight stressors↗
NASA NTRS1993

Gender differences in endocrine responses to posture and 7 days of 6 deg head down bed rest

Endocrine regulation of fluids and electrolytes during seven days of 6 deg head down bed rest (HDBR) was compared in male (n = 8) and, for the first time, female (n = 8) volunteers. The subjects' responses to quiet standing for 2 hr before and after HDBR were also tested. In both sexes, diuresis and natriuresis were evident during the first 2-3 days of HDBR, resulting in a marked increase in the urinary Na/K ratio and significant Na retention on reambulation. After the first day of HDBR, plasma renin activity (PRA) was increased relative to aldosterone, plasma volume was decreased, and the renal response to aldosterone appeared to be appropriate. Circulating levels of arginine vasopressin (AVP), cortisol, and ACTH were unchanged during HDBR. Plasma testosterone decreased slightly on day 2 of HDBR in males. The ratio of AM ACTH to cortisol was lower in females than in males because ACTH was lower in females. Urinary cortisol increased and remained elevated throughout the HDBR in males only. There were no gender differences in the responses to 7 day HDBR, except those in the pituitary-adrenal system; those differences appeared unrelated to the postural change. The provocative cardiovascular test of quiet standing before and after bed rest revealed both sex differences and effects of HDBR. There were significant sex differences in cardiovascular responses to standing, before and after HDBR. Females had greater PRA and aldosterone responses to standing before bedrest and larger aldosterone responses to standing after HDBR than males. Cardiovascular responses to standing before and after bedrest differed markedly: arterial pressure and heart rates increased with standing before HDBR, by contrast, arterial pressure decreased, with greater increases in heart rates after HDBR. In both sexes, all hormonal responses to standing were greater after HDBR. The results show clearly that similar responses to standing as well as to HDBR occur in both sexes, but that females exhibit greater PRA and aldosterone responses than males.

Vernikos, J.↗
NASA NTRS1995

Immune Alterations in Male and Female Mice after 2-Deoxy-D-Glucose Administration

Administration of 2-deoxy-D-glucose (2-DG), an analog of glucose which inhibits glycolysis by competitive antagonism for phosphohexose isomerase, results in acute periods of intracellular glucoprivation and hyperglycemia resulting in hyperphagia. In addition to these changes in the carbohydrate metabolism, injection of 2-DG results in alterations of both the endocrine and neurological systems as suggested by modifications in oxytocin and glucocorticoid levels and norepinephrine production. Moreover, alterations of the immune response, such as a decrease in the in vitro proliferation of splenocytes after mitogen-stimulation, were observed in mice injected with 2-DG. Sex, genotype and environment are among the factors that may modulate effects of catecholamines and hypothalamo-pituitary-adrenal axis on these immune changes. Sexual dimorphism in immune function resulting from the effects of sex hormones on immune effector cells has been shown in both animals and humans. These observations have important implications, especially with regard to higher incidence of many autoimmune diseases in females. Evidence exists that reproductive hormones influence the immune system and increase the risk of immunologically related disorders in both animals and humans. Indeed, immunological responses in stressful situations may also be confounded by fluctuations of sex hormones especially in females. Lymphocyte distribution, cytoldne production, and the ability of lymphocyte to proliferate in vitro were analyzed in male and female mice to determine if sex influenced 2-DG immunomodulation. In addition, the influence of hormones, especially sex hormones, on these changes were evaluated.

Dreau, Didier↗
NASA NTRS2010

60 Days of Head-down Bedrest Differentially Alters Venous Function in Lower and Upper Body Between Healthy Men and Women

The incidence of orthostatic intolerance after space flight is disproportionally higher in female compared to male crewmembers (83% vs. 20%). Experimental and human data suggest that the loss of orthostatic tolerance is due, at least in part, to microgravity-induced changes in venous compliance and that these changes are specific to the lower body. It is unknown however, whether the changes in venous compliance are different between males and females after space flight, and whether this is related to the disparity in orthostatic intolerance between the sexes. Using 6deg head-down bed rest (BR) as a model of space flight, we tested the following hypotheses; 1) females, compared to males, would experience a greater increase in venous compliance in dorsal foot veins as an effect of BR and 2) no differences in venous compliance would be found in dorsal hand veins between sexes and across BR days. Using 2-D ultrasound, dorsal hand (DHV) and foot vein (DFV) responses (diameter; expressed as sq mm) to 40 mmHg of congestion pressure (compliance) and to intravenous infusion of phenylephrine (PE; 3160ng/min) were determined in 10 females and 16 males before and after 60 days of BR. The relation between changes in vein diameter (in response to pressure and PE), sex, limb, and BR days were determined using a mixed-effect linear regression. It was found that after 60 days of BR, DFV dilator response to pressure was significantly greater in females and significantly less in males compared to pre-BR. As expected, there were no differences in DHV dilator response between sexes nor was there a significant difference between pre and post measures within groups. Notably, the venoconstrictor response to infusions of PE in the DHV and DFV where similar between sexes and across BR days. In conclusion, this study demonstrates that after 60 days of BR, dorsal foot veins are more compliant in women and less compliant in men. Moreover, the changes in lower body vein compliance in females do not appear to be due to changes in vasoconstrictor tone as their response to PE was preserved and similar to that in males. Taken together these data suggest that the higher incidence of orthostatic intolerance in females after space flight is due to increased venous compliance in the lower body which could translate to lower venous filling pressures and a reduced stroke volume.

Westby, Christian M.↗
NASA NTRS2019

Simulated Weightlessness Alters Cardiomyocyte Structure and Transcriptional Regulation of Mediators Related to Immunity and Cardiovascular Disease

Spaceflight and the ensuing fluid shifts, together with an overall reduction in physical activity, lead to acute and latent effects on the cardiovascular system. This current study makes use of the rodent hindlimb unloading (HU) model to determine how factors such as sex, age, and duration of exposure impact cardiac responses to weightlessness. We hypothesize that extended exposure to simulated weightlessness and the ensuing recovery alters cardiac structure and expression of select genes, including those involved in redox signaling which together, negatively impact long-term cardiac tissue health. To begin to test this hypothesis, male and female rats underwent HU at various durations up to 90 days, with a subset reambulated after 90 days of HU. Physiological stress or contractility changes lead to alterations in ventricular cardiomyocyte size and ventricular wall thickness to adapt to greater functional demand and mitigate mechanical stress to ventricular tissue; under certain conditions, these changes also may mark progression to cardiac failure. Hence, left ventricular cardiomyocyte size (cardiomyocyte cross sectional area, CSA) was quantified to determine if HU leads to structural adaptation responses in cardiac tissue and if age and sex had any impact on this outcome. Cardiomyocyte CSA of older males (9 months) were altered by HU in a time-dependent manner, where HU led to decreases in CSA at 14 days and increases at 90 days. In contrast, younger males (3 months) did not show any changes at day 14 of HU. CSA of females (3 months) was increased in response to short-term HU (14 days) suggesting sex-dependence of structural changes. In older HU males, cardiomyocyte CSA was comparable to controls after 90 days of re-ambulation. Levels of the DNA oxidative damage marker, 8-hydroxydeoxyguanosine (8-OHdG) were greater in left ventricular tissue of females that underwent HU compared to sex-matched controls, while there were no such differences in older or younger males. To gain insight into the signals that drive cardiac adaptations to HU, global transcriptomic analysis (RNAseq) was performed on left ventricular tissue of older males that underwent 14 days of HU. Short-term simulated weightlessness led to differential expression of genes involved in immune and pro-inflammatory signaling. A subset of these genes play a role in autoimmune and cardiovascular disease and are targets of current drugs used to treat bradycardia, hypertension, atherosclerosis and rheumatoid arthritis, amongst others. Oxidative damage/redox signaling pathways were not enriched at the timepoint tested in older males. Since young females displayed greater oxidative damage to DNA, activation of oxidative stress responses at earlier or later time points cannot be ruled out. In summary, simulated weightlessness in adult rats caused changes in cardiomyocyte structure in a sex and age-dependent manner, and the transcriptional regulation of key mediators of immunity and cardiovascular disease, meriting further study to define cardiac risks for interplanetary travel of human crew. Our findings also confirm the value of the rat HU model for cardiac health and countermeasure research.

Tahimic, Candice↗
NASA NTRS1994

Cardiovascular responses to postural changes: differences with age for women and men

The cardiovascular responses to postural change, and how they are affected by aging, are inadequately described in women. Therefore, the authors examined the influence of age and sex on the responses of blood pressure, cardiac output, heart rate, and other variables to change in posture. Measurements were made after 10 minutes each in the supine, seated, and standing positions in 22 men and 25 women who ranged in age from 21 to 59 years. Several variables differed, both by sex and by age, when subjects were supine. On rising, subjects' diastolic and mean arterial pressures, heart rate, total peripheral resistance (TPR), and thoracic impedance increased; cardiac output, stroke volume, and mean stroke ejection rate decreased; and changes in all variables, except heart rate, were greater from supine to sitting than sitting to standing. The increase in heart rate was greater in the younger subjects, and increases in TPR and thoracic impedance were greater in the older subjects. Stroke volume decreased less, and TPR and thoracic impedance increased more, in the women than in the men. The increase in TPR was particularly pronounced in the older women. These studies show that the cardiovascular responses to standing differ, in some respects, between the sexes and with age. The authors suggest that the sex differences are, in part, related to greater decrease of thoracic blood volume with standing in women than in men, and that the age differences result, in part, from decreased responsiveness of the high-pressure baroreceptor system.

Posture/physiology↗
NASA NTRS1977

Comparison of hormone and electrolyte circadian rhythms in male and female humans

Circadian rhythm characteristics in healthy male and female humans were studied at 4-hour intervals for urine volume, cortisol, 5-hydroxyindoleacetic acid (5-HIAA), Na, K, Na/K ratios in the urine, as well as plasma cortisol. While plasma and urinary cortisol rhythms were very similar in both sexes, the described rhythms in urine volume, electrolyte, and 5-HIAA excretion differ for the two sexes. The results suggest that sex differences exist in the circadian patterns of important hormone and metabolic functions and that the internal synchrony of circadian rhythms differs for the two sexes. The results seem to indicate that the rhythmical secretion of cortisol does not account for the pattern of Na and K excretion.

Vernikos-Danellis, J.↗
NASA NTRS2016

Risk of Performance Decrements and Adverse Health Outcomes Resulting from Sleep Loss, Circadian Desynchronization, and Work Overload

Sleep loss, circadian desynchronization, and work overload occur to some extent for ground and flight crews, prior to and during spaceflight missions. Ground evidence indicates that such risk factors may lead to performance decrements and adverse health outcomes, which could potentially compromise mission objectives. Efforts are needed to identify the environmental and mission conditions that interfere with sleep and circadian alignment, as well as individual differences in vulnerability and resiliency to sleep loss and circadian desynchronization. Specifically, this report highlights a collection of new evidence to better characterize the risk and reveals new gaps in this risk as follows: Sleep loss is apparent during spaceflight. Astronauts consistently average less sleep during spaceflight relative to on the ground. The causes of this sleep loss remain unknown, however ground-based evidence suggests that the sleep duration of astronauts is likely to lead to performance impairment and short and long-term health consequences. Further research is needed in this area in order to develop screening tools to assess individual astronaut sleep need in order to quantify the magnitude of sleep loss during spaceflight; current and planned efforts in BHP's research portfolio address this need. In addition, it is still unclear whether the conditions of spaceflight environment lead to sleep loss or whether other factors, such as work overload lead to the reduced sleep duration. Future data mining efforts and continued data collection on the ISS will help to further characterize factors contributing to sleep loss. Sleep inertia has not been evaluated during spaceflight. Ground-based studies confirm that it takes two to four hours to achieve optimal performance after waking from a sleep episode. Sleep inertia has been associated with increased accidents and reduced performance in operational environments. Sleep inertia poses considerable risk during spaceflight when emergency situations necessitate that crewmembers wake from sleep and make quick decisions. A recently completed BHP investigation assesses the effects of sleep inertia upon abrupt awakening, with and without hypnotics currently used in spaceflight; results from this investigation will help to inform strategies relative to sleep inertia effects on performance. Circadian desynchrony has been observed during spaceflight. Circadian desynchrony during spaceflight develops due to schedule constraints requiring non-24 operations or 'slam-shifts' and due to insufficient or mis-timed light exposure. In addition, circadian misalignment has been associated with reduced sleep duration and increased medication use. In ground-based studies, circadian desynchrony has been associated with significant performance impairment and increased risk of accidents when operations coincide with the circadian nadir. There is a great deal of information available on how to manage circadian misalignment, however, there are currently no easily collected biomarkers that can be used during spaceflight to determine circadian phase. Current research efforts are addressing this gap. Work overload has been documented during current spaceflight operations. NASA has established work hour guidelines that limit shift duration, however, schedule creep, where duty requirements necessitate working beyond scheduled work hours, has been reported. This observation warrants the documentation of actual work hours in order to improve planning and in order to ensure that astronauts receive adequate down time. In addition to concerns about work overload, ground based evidence suggests that work underload may be a concern during deep space missions, where torpor may develop and physically demanding workload will be exchanged for monitoring of autonomous systems. Given that increased automation is anticipated for exploration vehicles, fatigue effects in the context of such systems needs to be further understood. Performance metrics are needed to evaluate fitness-for-duty during spaceflight. Although ground-based evidence supports the notion that sleep loss, circadian desynchronization and work overload lead to performance impairment, inconsistency in the measures used to evaluate performance during spaceflight make it difficult to evaluate the magnitude of performance impairment during spaceflight. Work is underway to standardize measures of performance evaluation during spaceflight. Once established, such performance indicators need to be correlated with operational performance. Individual differences in sleep need and circadian preference, phase shifting ability and period have been documented in ground-based studies. Individual differences in response to sleep loss and circadian misalignment have also been documented and are presumed to be associated with genetic polymorphisms. No studies have systematically reported individual differences in sleep or circadian-related outcomes during spaceflight. More work is needed in this area in order to identify genetic or phenotypic biomarkers that predict resilience or vulnerability to sleep loss in order to personalize countermeasure strategies and mitigate performance impairment during spaceflight. Two laboratory and field investigations specific to this topic are currently ongoing; additional efforts, including an effort to mine existing biological data from spaceflight relative to sleep and circadian outcomes, are planned. Sex differences in sleep need and circadian period and phase have been reported in ground-based studies. The impact of these sex differences on performance is unclear. Sex differences in sleep need and circadian rhythms have not been systematically studied during spaceflight, presumably due to the small number of women that have flown in space. More research is needed in this area to evaluate whether any of the observed sex differences in physiology lead to altered performance in spaceflight and on the ground.

Flynn-Evans, Erin↗
NASA NTRS1993

Gender differences in endocrine responses to posture and 7 days of -6 degrees head-down bed rest

Endocrine regulation of fluids and electrolytes during 7 days of -6 degrees head-down bed rest (HDBR) was compared in male (n = 8) and, for the first time, female (n = 8) volunteers. The subjects' responses to quiet standing for 2 h before and after HDBR were also tested. In both sexes, diuresis and natriuresis were evident during the first 2-3 days of HDBR, resulting in a marked increase in the urinary Na(+)-to-K+ ratio and significant Na+ retention on re-ambulation. After the 1st day of HDBR, plasma renin activity (PRA) was increased relative to aldosterone (Aldo), plasma volume was decreased, and the renal response to Aldo appeared to be appropriate. Circulating levels of arginine vasopressin, cortisol, and ACTH were unchanged during HDBR. Plasma testosterone decreased slightly on day 2 of HDBR in males. The ratio of early morning ACTH to cortisol was lower in females than in males because ACTH was lower in females. Urinary cortisol increased and remained elevated throughout the HDBR in males only. There were no gender differences in the responses to 7 days of HDBR, except those in the pituitary-adrenal system; those differences appeared unrelated to the postural change. The provocative cardiovascular test of quiet standing before and after HDBR revealed both sex differences and effects of HDBR. There were significant sex differences in cardiovascular responses to standing before and after HDBR. Females had greater PRA and Aldo responses to standing before HDBR and larger Aldo responses to standing after HDBR than males.(ABSTRACT TRUNCATED AT 250 WORDS).

NASA Discipline Number 14-10↗
NASA NTRS2016

Variation in Nest Temperatures of the American Alligator Found on the Kennedy Space Center Merritt Island National Wildlife Refuge

Information on nest temperatures of the American Alligator (Alligator mississippiensis) constructed in the wild is limited. Nesting temperatures during a critical thermal sensitive period determine the sex of alligators and are therefore critical in establishing the sex biases in recruitment efforts of alligators within a given community. Nest components, varying environmental conditions, and global warming could have a significant impact on nest temperatures, thus affecting future generations of a given population. One hundred and seventy four programmable thermistors were inserted into fifty eight nests from 2010 through 2015 nesting cycles. Three thermistors were placed inside each nest cavity (one on top of the eggs, one in the middle of the eggs, and one at the bottom of the clutch of the eggs) to collect temperature profiles in the incubation chamber and throughout the entire incubation period. One thermistor was also placed near or above these nests to obtain an ambient air temperature profile. Once retrieved, data from these thermistors were downloaded to examine temperature profiles throughout the incubation period as well as during the period of sexual determination. These data would help establish survival rates related to nest temperature and predict sex ratio of recruited neonates at the Kennedy Space Center. Over three million temperatures have been recorded since 2010 for the alligator thermistor study giving us insight to the recruitment efforts found here. Precipitation was the largest influence on nesting temperatures outside of daily photoperiod, with immediate changes of up to eight degrees Celsius.

Alligator↗
NASA NTRS2024

Long-term effects of acute irradiation and isolation on crew age-matched mice

The future of space missions beyond low-Earth orbit presents exciting opportunities but may come with formidable health challenges. Astronauts face a unique combination of space stressors capable of exerting effects on the central nervous system (CNS) with possible sex-dependent differences. The interaction of these combined spaceflight stressors may induce oxidative stress, thereby altering brain integrity and behavioral performance. Understanding these changes is critical for safeguarding astronaut health and enabling successful exploration. By understanding the physiological responses to the combined effects of ionizing radiation (IR) and social isolation in the brain through immunohistochemistry (IHC), proteomics and cytokine expression analyses, we aim to identify CNS pathways ripe for countermeasure development to mitigate adverse brain changes with future deep space exploration. Here, we study the combined effects of simulated 5-ion galactic cosmic radiation (GCRsim) at acute dosage (5, 15, and 50 cGy) and social isolation on crew age-matched male and female mice at 124 days post-irradiation. We conducted analyses of hippocampal cytokine biomarkers and proteomic profiling on hippocampal lysates. Our findings reveal sex-specific regulation of hippocampal cytokines and proteomic profiles. Ongoing immunohistochemistry findings on the hippocampus will provide qualitative information regarding key protein expression and cellular changes such as microglial activation, blood brain barrier integrity, and neuroinflammation. With future plans for long-duration space missions, such as Mars exploration, understanding CNS changes over extended periods in mice can provide insights into potential long-term health impacts on astronauts. This project will provide us with valuable insights into sex-differences in neurobiological processes and disease mechanisms impacting men and women in space.

space radiation↗
NASA NTRS1974

An analysis of job placement patterns of black and non-black male and female undergraduates at the University of Virginia and Hampton Institute

Research questions were proposed to determine the relationship between independent variables (race, sex, and institution attended) and dependent variables (number of job offers received, salary received, and willingness to recommend source of employer contact). The control variables were academic major, grade point average, placement registration, nonemployment activity, employer, and source of employer contact. An analysis of the results revealed no statistical significance of the institution attended as a predictor of job offers or salary, although significant relationships were found between race and sex and number of job offers received. It was found that academic major, grade point average, and source of employer contact were more useful than race in the prediction of salary. Sex and nonemployment activity were found to be the most important variables in the model. The analysis also indicated that Black students received more job offers than non-Black students.

Anderson, A. F.↗
NASA NTRS1975

Demographic and psychological variables affecting test subject evaluations of ride quality

Ride-quality experiments similar in objectives, design, and procedure were conducted, one using the U.S. Air Force Total In-Flight Simulator and the other using the Langley Passenger Ride Quality Apparatus to provide the motion environments. Large samples (80 or more per experiment) of test subjects were recruited from the Tidewater Virginia area and asked to rate the comfort (on a 7-point scale) of random aircraft motion typical of that encountered during STOL flights. Test subject characteristics of age, sex, and previous flying history (number of previous airplane flights) were studied in a two by three by three factorial design. Correlations were computed between one dependent measure, the subject's mean comfort rating, and various demographic characteristics, attitudinal variables, and the scores on Spielberger's State-Trait Anxiety Inventory. An effect of sex was found in one of the studies. Males made higher (more uncomfortable) ratings of the ride than females. Age and number of previous flights were not significantly related to comfort ratings. No significant interactions between the variables of age, sex, or previous number of flights were observed.

Duncan, N. C.↗
NASA NTRS2001

The Effect of Hindlimb Suspension on the Reproductive System of Young Male Rats

Colonization of space requires the ability to reproduce in reduced gravity. Following spaceflight, astronauts and male rats exhibit decreased testosterone (T). This has important implications as T effects the testes and accessory sex glands. To our knowledge no studies have examined the effects of spaceflight on accessory sex glands. Due to the rarity of spaceflight opportunities, ground models have been used to simulate weightlessness. The objective of this study was to determine the effect of long-term (21 d) weightlessness on the reproductive system of male rats. Weightlessness was simulated using the Morey-Holton hindlimb suspension (HLS) model. Age 10 week old, male Sprague-Dawley rats weighing (209.0 +9.7g) were randomly assigned (n=10/group) to either HLS or ambulatory control. In HLS rats, testes mass was 33% lower (p<0.05) than ambulatory controls. However, HLS had no effect on prostate (0.65 +0.09g vs 0.69 +0.12g) or seminal vesicles (1.01 +0.35g vs 0.75 +0.22g) weights compared to controls. The absence of effects on plasma T in this study contrasts previous reports of reduced plasma T in HLS male rats. This discrepancy may have been due to the age of animal and timing of sampling. T levels vary dramatically during testes development as well as within normal diurnal cycles. In young HLS rats, testes weight was reduced but not plasma T. Subsequently there was no effect on accessory sex glands. However, this may not be the case in older rats. More studies using standardized methods are needed to gain a better understanding of male reproduction function and capability in weightlessness. Funding provided by NASA.

Tou, Janet↗
NASA NTRS2009

Gender-related Changes in Dorsal Hand and Foot Vein Function Following 60 Days of Head Down Bed Rest

It is well known that female astronauts are more likely to experience post-flight orthostatic hypotension and presyncope compared to male astronauts. It has been suggested that the disproportionally higher incidence of presyncope (83% of female vs. 20% male crewmembers) may be due to sex-related differences in vascular function between the upper and lower limbs. However, much of this evidence is specific to changes in resistance vessels. Given that more than 70% of the circulating blood volume resides in compliance vessels, it is conceivable that even small changes in venous function may contribute to post-flight orthostatic hypotension. In spite of this, little is currently known regarding the influence of microgravity exposure on venous function between males and females. PURPOSE: To determine the influence of 60 days of HDBR on dorsal foot and hand vein function between healthy males (M) and females (F). METHODS: Using 2-D ultrasound, dorsal hand and foot vein diameter responses to intravenous infusions phenylephrine (PE), acetylcholine (ACh), and nitroglycerine (NTG) were determined in 26 adults; 10 females (age:37 +/- 2 yr ) and 16 males (age:34 +/- 2 yr ). Changes in venous function were calculated as the difference between diameter at baseline and following each venoactive drug. Differences in venous function between limb and sexes across HDBR were determined using mixed-effects linear regression. RESULTS: In response to 60 days of HDBR, the change in venousconstrictor response to PE in the dorsal hand veins was not significantly different between M and F. Interestingly, the change in constrictor response in the dorsal foot veins (compared to pre HDBR) was approximately 30% greater in the F, whereas the constrictor response was approximately 45% less in the M (p=0.026). HDBR had no influence on the change in dilator response to ACh, or NTG between M and F and between vascular beds. CONCLUSION: These results demonstrate that 60 days of HDBR contributes to sex-related differences in venous function. Importantly, the changes are specific to dorsal foot veins and do not appear to be related to changes in endothelial or smooth muscle function. Previous data from our laboratory indicate that females have an impaired sympathetic response following HDBR. However, the results from the current investigation imply that F maintain the ability to respond to sympathetic stimulation but may not be able to adequately activate a proper response following HDBR.

Westby, Christian M.↗
NASA NTRSDate not supplied

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↗
NASA NTRSDate not supplied

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↗
NASA NTRSDate not supplied

The Effects of Spaceflight and Microgravity Exposure on Female Astronaut Health and Performance

Over the past half century, our understanding of the physiological effects of space exploration and microgravity exposure have improved immensely. Microgravity causes incredible changes to the human body that increase risk of injury upon return to Earth and lunar/planetary egress scenarios. This is due to deconditioning of the cardiovascular and skeletal muscle systems that reduce aerobic capacity and muscular strength. With upcoming exploration class missions, such as NASA’s Artemis lunar exploration program which aims to send the first female astronaut to the lunar surface by 2030, as well as a long-term goal of Martian exploration, maintaining astronaut health during extended-duration space flight is critical for achieving mission objectives. However, our understanding of these physiological implications due to microgravity are based primarily on flight studies of male astronauts and 1g bedrest analog study participants, with few investigations focusing specifically on females. Innate physiologic differences in endocrine signaling and reproductive function impact sex-dependent responses to various health conditions, treatments, and environmental factors in nearly every system in the body. Therefore, to assume comparable alterations in females in response to microgravity exposure may be inappropriate and consequentially, could lead to lasting impacts on female astronaut health and impact mission success. Moreover, differences in sex hormones may also influence the regulation of cardiovascular control during egress activity after space flight-induced deconditioning and blood volume loss (i.e., risk for orthostatic intolerance). Other potential physiological systems and factors related to musculoskeletal health and aerobic capacity that warrant investigation with respect to microgravity include endocrine/reproductive function, vascular control, bone mineral density/microarchitecture, and soft-tissue health. The purpose of this investigation is two-fold: 1) to summarize the data available from space flight and simulated bedrest analog exposures to begin addressing these gaps in knowledge regarding impacts to female astronaut health, and 2) to describe differences in demographic health characteristics, injury prevalence, and aerobic capacity and muscular strength in NASA female and male astronauts. Female astronauts make up 50% of Artemis-specific astronaut corps and the extent to which microgravity exposure impacts female cardiovascular and musculoskeletal health, and whether these alterations are consistent with their male counterparts, is inconclusive. With the growing inclusion of female astronauts in the NASA space program and the increased duration of missions beyond low Earth orbit, a greater understanding of the sex-specific adaptation to space travel will help determine the development of appropriate countermeasures for minimizing risk and maintaining health of all astronauts.

Nicole Christine Strock↗