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All sourcesNASA NTRSDOE OSTI
NASA NTRS2017

Intrauterine Exposure to Maternal Stress Alters Bdnf IV DNA Methylation and Telomere Length in the Brain of Adult Rat 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 contribute to the long-term effects of intrauterine exposure to maternal stress on offspring behavioral outcomes. 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 rat male and female offspring whose mothers were exposed to unpredictable and variable stressors throughout gestation. Males exposed to prenatal stress had greater methylation (Bdnf IV) in the medial prefrontal cortex (mPFC) compared to non-stressed controls. Further, prenatally-stressed males had shorter telomeres than controls in the mPFC. This study provides the first evidence in a rodent model of an association between prenatal stress exposure and subsequent shorter brain telomere length. Together findings indicate a long-term impact of prenatal stress on DNA methylation and telomere biology with relevance for behavioral and health outcomes, and contribute to a growing literature linking stress to intergenerational epigenetic alterations and changes in telomere length.

prenatal stress↗
NASA NTRS2016

Unpredictable Variable Prenatal Stress Programs Expression of Genes Involved in Appetite Control and Energy Expenditure

Exposure to stress in the womb shapes neurobiological and physiological outcomes of offspring in later life, including body weight regulation and metabolic profiles. Our previous work utilizing a centrifugation-induced hypergravity demonstrated significantly increased (8-15) body mass in male, but not female, rats exposed throughout gestation to chronic 2-g from conception to birth. We reported the same outcome in adult offspring exposed throughout gestation to Unpredictable Variable Prenatal Stress (UVPS). Here we examine gene expression changes using our UVPS model to identify a potential role for prenatal stress in this hypergravity programming effect. Specifically we focused on appetite control and energy expenditure pathways in prenatally stressed adult (90-day-old) male Sprague-Dawley rats. Time-mated female rats were exposed throughout their 22-day pregnancy to UVPS consisting of white noise, strobe light, and tube restraint individually once per day on an unpredictable schedule for 15, 30 or 60 min. To control for potential changes in postnatal maternal care, newborn pups were fostered to non-manipulated, newly parturient dams. At 90-days of age, we analyzed plasma concentrations of hormones involved in appetite control and energy expenditure (leptin and adiponectin), and quantified expression of key genes in epididymal fat pads harvested from adult male offspring and controls. Leptin regulates energy balance by inhibiting hunger, and adiponectin modulates glucose levels and fatty acid breakdown. Our findings indicate significantly elevated plasma leptin concentrations and reduced expression of epididymal fat leptin (OB) and adiponectin (ADIPOQ) genes compared to controls. Analyses presently underway include quantification of plasma insulin and glucose, and the expression of ghrelin, a peptide that acts on the central nervous system and the body's perception of hunger. Collectively, these findings will further understanding of the consequences of UVPS on body weight regulation and metabolism, and provide further insight into the effect of gravity modulation on mammalian fetal development.

Appetite Control↗
NASA NTRS2018

The Evaluation of Anthropomorphic Test Device Response under Vertical Loading

During the winter of 2018, a series of vertical tests was conducted on three sizes of Anthropomorphic Test Devices (ATDs) for the evaluation of their vertical loading response. The three sizes of ATDs represented a 5th percentile female, a 50th percentile male, and a 95th percentile male. There were two variations of the 50th percentile male as defined in 49 CFR Part 572: a Hybrid II and an FAA Hybrid III. Tests were conducted on a drop tower located at NASA Langley Research Center’s (LaRC) Landing and Impact Research (LandIR) Facility. The ATDs were seated on 14 CFR § 25.562 certified seats, in either a triple (window, middle and aisle) or a double (window and aisle) seat configuration, with seat leg spacing replicating a Fokker F28 MK-1000 aircraft. The seat and ATDs were attached to a drop plate on the tower, which was lifted to a height of 14 ft. The system was dropped onto different sections of crushable foam wedges to achieve multiple input deceleration environments. The purpose of the tests was to evaluate the differences in lumbar response, to examine scaling characteristics from sizing factors in the ATDs, and also to compare the results to computer simulation efforts. Results will be presented and comparisons will be discussed.

Anthropomorphic Test Devices (ATDs)↗
NASA NTRS2016

Advances in Rodent Research Missions on the International Space Station

A Research platform for rodent experiment on the ISS is an essential tool for advancing biomedical research in space. The Rodent Research allows for experiments of much longer duration that experiments on the Shuttle. NASA’s Rodent Research (RR)-1 mission was successfully completed, including post-flight analysis and achieved a number of objectives including validation of flight hardware, on-orbit operations, and science capabilities that were developed at the NASA Ames Research Center. Briefly, twenty C57BL/6J adult female mice were launched on the SpX4 Dragon vehicle, which thrived for up to 37 days in microgravity. Daily health checks of the mice were performed during the mission via downlinked video; all animals were healthy and displayed normal behavior without any significant signs of stress. Behavioral analysis demonstrated that Flight and Ground Control mice exhibited the same range of behaviors, including eating, drinking, exploratory behavior, self- and allo-grooming, and social interactions indicative of healthy animals. The animals were euthanized and select tissues were collected from some of the mice on orbit to assess the long-term sample storage capabilities of the ISS. The data obtained from the flight mice were comparable to those from the 3 groups of control mice (baseline, vivarium and ground controls), suggesting that the ISS has adequate capability to support long-duration rodent experimentations. We recovered over 35 tissues from 40 RR1 frozen carcasses, yielded over 3200 aliquots of tissues, and distributed to the scientific community, including NASA’s GeneLab and scientists in the U.S. through Biospecimen Sharing Program via Ames Life Science Data Archive. Tissues were also distributed to Russian research colleagues at the Institute for Biomedical Problems. The expression levels of select genes including albumin, catalase, GAPDH, HMGCoA Reductase, and IGF1 were determined using RNA isolated from the livers by qPCR and no significant differences by one factor ANOVA were found between flight and ground control groups. In addition, some of the liver samples were subject to transcriptomics, epigenomics and proteomics. The data are now available to the scientific community through GeneLab’s open science data website. Since the RR1 mission, another long duration mission (Rodent Research-2) was completed on the ISS in 2015 in which 20 female C57 BL/6J mice were successfully maintained on the ISS for varying time points, with the last group of 5 animals being on-orbit for 54 days. This second Rodent Research flight expanded the program’s capabilities with the introduction of new technologies including blood collection and separation and bone densitometry scanning. Furthermore, we have continued to expand the ISS’s capabilities by running a series of ground-based verification testing using male mice. Our next step is to fly male mice for Rodent Research-4 on SpaceX-10 to study the effects of microgravity on bone healing and regeneration. It will be the first long-duration mission using male mice using Rodent Hardware. In addition, the number of mice will increase from 20 mice (on RR-1 and RR-2) to 40 for RR-4. When samples return to Earth, a number of tissues will be dissected from the frozen carcasses and select tissue samples will become available to the scientific community via BSP. Altogether, we have continued to expand our capabilities for performing long-duration missions on the ISS as emphasized in the National Research Council’s Decadal Survey released in 2011 and to maximize science return from each mission.

Choi, S.↗
NASA NTRS2019

Development of a Novel Helmet Support Assembly for NASA Orion Crew Survival Suit

Orion Spacecraft water landing environments have necessitated the design and testing of a novel Helmet Support Assembly (HSA) as part of the NASA Orion Crew Survival Systems (OCSS) launch and re-entry spacesuit. A series of development sled tests using 5 th female, 50th male, and 95th male Hybrid III Anthropometric Test Devices (ATDs) simulated worst case water landings and identified the need for an integrated suit countermeasure to control the helmet during dynamic loading. Initial prototype countermeasures rigidly restrained the helmet keeping the helmet in place as desired, but led to large force and moment transmission to the upper neck. Further development led to a flexible HSA which used high-strength steel wire contoured to the size-matched ATD thorax and attached to both the front and rear of the neck ring. The selected wire diameter and contoured shape provided some ability to flex under the expected worst-case dynamic loads. The existing shoulder harness was used to restrain the helmet motion during “eyeballs out/down” loading while also attempting to prevent head-to-helmet contact in “eyeballs down” spinal-axis loading. A new small prototype helmet was also developed and tested for the 5th and 50th ATDs with both HSA devices. Dynamic impact tests were conducted on the HIA (Horizontal Impulse Accelerator) at Wright Patterson Air Force Base (WPAFB) under simulated off-nominal landing conditions using a representative Orion seat and 5-point harness. For each ATD size, peak Neck Injury Criteria (Nij) were compared to equivalent sled tests with an unsuited ATD configuration. Adding a helmet without attempting to control motion increased peak Nij values for all ATD sizes. The use of the rigid countermeasure showed decreased peak Nij results for the 5th female, but increased peak Nij values for both 50th configurations and the 95th male ATDs. By comparison, the flexible HSA showed reduced peak Nij values for all ATD sizes. Overall, this series of dynamic impact tests identified a risk of increased crew neck loading when under- or over-restraining the helmet during simulated Orion water landings and also demonstrated an effective strategy to mitigate those loads with a compliant HSA design.

Safety↗
NASA NTRS2021

Comparing Theoretically Scaled Biomechanical Models

BACKGROUND An investigation into incorporating space suit aspects required a 50th-percentile male model which was not part of the existing dataset of models. Previously, theoretical models for 5th-percentile female and 95th-percentile male were created utilizing a scaled test subject as close as possible to the target height and weight. Scaling factors were created by taking the height ratio and applying it uniformly to the model body segments, then fine tuning to ensure the theoretical model’s height is as expected. This study was initiated to examine the existing method of isometrically scaling in OpenSim [1,2] and to create alternative methods which do not rely on an existing subject being close in height and weight to the theoretical model of interest. Generating a theoretical biomechanical model provides additional abilities without the reliance on available OpenSim models or real subjects. Gained abilities include creating different percentile models and attaining representative anthropometry for any target height/weight, such as targeting specific crew populations or gaps within the current dataset. METHODS AND RESULTS This study includes 3 methods for generating the theoretical model; utilizing the modified unscaled OpenSim Full Body Rajagopal Model (FBRM) [3,4], a dataset of scaled OpenSim models, and existing scaling factors from Dumas et al. [5]. All methods use the Anthropometric Survey of US Army Personnel (ANSUR II) [6] as an input of necessary anthropometric measurements. The following measurements are retrieved from the ANSUR II collection: mass, stature, cervicale height, acromial height, axilla height, waist height, trochanterion height, lateral femoral epicondyle height, lateral malleolus height, acromion-radiale length, radiale-stylion length, palm length, ball of foot length, bicristal breadth, bimalleolar breadth. Some of the measurements are direct segment lengths and others are utilized to derive segment lengths. Height, weight, and age ranges are the required inputs to parse the collection for a mean value of the measurements. A simple iterative process may be necessary for the output of mean mass and stature consistent with the theoretical model of interest. In some cases, one may specify exact values instead of a range but that is dependent upon whether those exact values pertain to a single subject from the ANSUR II collection. Equations from Dumas et al. were used to calculate scaling factors for the two methods that utilize OpenSim scaled and unscaled models. In the third method, Dumas’ scaling factors were used directly instead of generating our own. After scaling factors are achieved, they are applied along with the mass and segment lengths retrieved from ANSUR II in order to calculate the segment mass, Center of Mass (CoM), mass Moment of Inertia (MoI), and the joint location in the parent frame. The theoretical models from the different methods were compared to the previous existing method of isometrically scaling in OpenSim, as well as the standards found in NASA STD-3000 [7] and the NASA Human Integration Design Handbook [8]. The whole-body center of mass is the main comparison performed between the models and the standards. The body segment mass properties were also compared when possible. In some cases, the standards do not provide complete data, or the center of mass location is not provided with respect to the appropriate joint coordinate system. For a 50th-percentile male subject, results from isometric scaling in OpenSim and the method utilizing the unscaled FBRM were compared to the standards in NASA STD-3000. According to the standard, the whole-body vertical CoM location was taken from the head vertex to the CoM. The standards provide 80.2 cm for the CoM vertical component whereas isometric scaling in OpenSim and utilizing the unscaled FBRM provide 82.2 and 82.3 cm, respectively. Through definition, the whole-body CoM in the medial/lateral direction agreed across the models. Investigation is on-going to clearly identify the reference point pertaining to dorsal/ventral whole-body CoM position in standards and relate that to the theoretical models. REFERENCES [1] Delp, S.L., et al., “OpenSim: Open-source Software to Create and Analyze Dynamic Simulations of Movement”, IEEE Transactions on Biomedical Engineering, (2007). [2] Seth, A., Hicks J.L., Uchida, T.K., Habib, A., Dembia, C.L., Dunne, J.J., Ong, C.F., DeMers, M.S., Rajagopal, A., Millard, M., Hamner, S.R., Arnold, E.M., Yong, J.R., Lakshmikanth, S.K., Sherman,n M.A., Delp, S.L. OpenSim: Simulating musculoskeletal dynamics and neuromuscular control to study human and animal movement. Plos Computational Biology, 14(7). (2018) [3] R. K. Huffman, W. K. Thompson, C. A. Gallo, L. J. Quiocho, “Improvement of Scaling and Inverse Kinematic Results with Additional Upper Body Joints Added to Opensim Rajagopal Model”, NASA Human Research Program Investigator’s Workshop, (2019). [4] Huffman R.K., Thompson W., Gallo C., “Modified OpenSim Rajagopal Full Body Model”, New Technology Report, MSC-26872-1. (August 2020). [5] Dumas R., Cheze L. and Verriest J., 2007. “Adjustments to McConville et al. and Young et al. body segment inertial parameters”. Journal of Biomechanics 40, pp. 543-553 [6] Gordon C.C., 2012 “Anthropometric Survey of U.S. Army Personnel: Methods and Summary Statistics”, US Army Natick Soldier RD&E Center. [7] NASA STD-3000/REV-B, 1995. “The Man-System Integration Standards” [8] NASA/SP-2010-3407/REV-1, 2014. “The Human Integration Design Handbook (HIDH)”

F N Matari↗
NASA NTRSDate not supplied

Oxidative Stress and Neuroconsequences of the Spaceflight Environment –A 5-ion GCRsim Dose-response Study

The overall scope of this project is to test the hypothesis that Ionizing Radiation (IR), microgravity and social isolation combine synergistically to trigger an oxidative stress response that alters immune homeostasis, brain structure/function, and neurobehavioral/cognitive performance. Specific Aims for this project are to: (1) Determine dose-response curves for acute ‘Five-Ion GCR Simulation’ exposure for immune, brain and performance responses in crew age-matched adult male and female mice; (2) Determine effects of acute ‘Five-Ion GCR Simulation’ exposure singly and in combination with simulated microgravity and social isolation, on immune, brain and performance responses in crew age-matched male and female mice mimicking deep space missions; and (3) Determine efficacy of the dietary antioxidant, Nicotinamide Mononucleotide (NMN), a key intermediate in nicotinamide adenine dinucleotide (NAD+) biosynthesis. Here we exposed mature (23-24-week-old) male and female mice to simulated 5-Ion GCR (either 0, 5, 15, or 50cGy) at the NASA Space Radiation Laboratory (NSRL). Across ‘Acute’ (IR+72hrs and IR+14 days) and ‘Delayed’ (IR+28 to IR+124 days) phases of the 6-month-long study, we assessed immune, neural, and functional (sensorimotor/behavioral/cognitive) responses anticipated during a transit to Mars. This presentation will report on dose-response curves for 5-ion GCRsim related to potential biomarkers; structural/functional changes in the immune and nervous systems; and behavioral/cognitive performance deficits. This project addresses NASA’s efforts to characterize risks and identify appropriate countermeasures in anticipation of future deep space missions. Ensuring crew health and performance during extended transits necessitates that sensorimotor and cognitive abilities remain strong to avoid potentially catastrophic health and safety outcomes.

deep space↗
NASA NTRSDate not supplied

Sex differences and deep space stressors: effects of 5-ion gcrsim, simulated microgravityand social isolation on immune function, brain, and behavior in mice

This project is testing the hypothesis that Ionizing Radiation (IR), microgravity and social isolation combine synergistically to trigger an oxidative stress response that alters immune homeostasis, brain structure/function, and neurobehavioral/cognitive performance. Specific Aims for this project are to: (1) Determine dose-response curves for acute ‘Five-Ion GCR Simulation’ exposure for immune, brain and performance responses in crew age-matched adult male and female mice; (2) Determine effects of acute ‘Five-Ion GCR Simulation’ exposure singly and in combination with simulated microgravity and social isolation, on immune, brain and performance responses in crew age-matched male and female mice mimicking deep space missions; and (3) Determine efficacy of the dietary antioxidant, Nicotinamide Mononucleotide (NMN), a key intermediate in nicotinamide adenine dinucleotide (NAD+) biosynthesis. Here we report findings from our studies of mature (24-week-old) male and female mice exposed to simulated 5-Ion GCRsim (0, 5, 15, or 50cGy) at the NASA Space Radiation Laboratory (NSRL) followed by combinatorial exposures to 15cGy, simulated microgravity via head-down tilt (hindlimb unloading) and social isolation. Immune, brain and behavioral (sensorimotor, risk-taking & cognitive) measures were acquired at ‘Acute’ (IR+24hrs, IR+72hrs), ‘Intermediate’ (IR+14 days) and ‘Delayed’ (IR+28 to IR+124 days) to inform biological responses anticipated during a transit to Mars. This project addresses NASA’s efforts to characterize risks and identify appropriate countermeasures in both women and men in anticipation of future deep space missions. Ensuring crew health and performance during extended transits necessitates that sensorimotor and cognitive abilities remain strong to avoid potentially catastrophic health and safety outcomes. Supported by the NASA Human Research Program (HRP) Human Factors Behavioral Performance Element Grant 18 18FLAG 2 0028.

behavioral sciences↗
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↗
NASA NTRS2023

The Effects of Space Flight 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 bed rest 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 bed rest 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.

Female Astronaut↗
NASA NTRSDate not supplied

Neuro-behavioral Consequences of Low Dose Radiation Social Isolation and Sex Differences in the Longevity MCAT Mouse Model

The physiological responses to spaceflight elicit wide-ranging consequences and resemble aspects of aging on Earth. Previous studies have shown that oxidative damage via reactive oxygen species (ROS), contributes to aging-related pathologies. Our study uses 1-year old C57BL/6NJ male and female mice (astronaut-relevant age) that underwent exposure to 0.5 gray of gamma radiation together with social isolation and were euthanized 12 weeks after. We used the longevity MCAT mouse model in which human catalase is overexpressed in the mitochondria, for ROS quenching. We aimed to determine whether in older mice quenching ROS, will mitigate the neuro-behavioral consequences of low dose ionizing radiation and/or social isolation and whether the outcomes will differ in males and females. We have performed five mission relevant behavioral tests which focused on performance, memory, physical stance, and stress. We have detected both sex and radiation effects; the 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 indeed mitigated in the MCAT mice, pointing out to the importance of ROS in response to radiation stress and social isolation. We have measured plasma (7- and 90-days post radiation), cytokines, corticosterone and hippocampal cytokine and microglial activation at the end of the experiment. We saw significant changes in the plasma markers due to radiation, sex, and genotype in both short and long post radiation period and detected long term sex and radiation effects in the brain. Our focus is now on applying advanced statistical modeling to corelate the behavioral tests with our recent molecular findings to look for specific biomarkers that could predict behavioral deficits.

radiation↗
NASA NTRSDate not supplied

The Effects of Space Flight 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 bed rest 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 bed rest 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.

Female Astronaut↗
NASA NTRS2003

Exercise load index and changes in body weight during long-duration confinement in an isolated environment

PURPOSE: The objectives of this project were to investigate exercise load and body weight related to long-duration confinement in a closed environment simulating ISS flight conditions, and to evaluate subjects' motivation to continue the experiment and their adaptation to isolation. METHODS: Four Russian male subjects participated in a 240-d experiment (Group I), and four subjects (three male subjects and one female subject) from Austria, Canada, Japan, and Russia participated in a 110-d experiment (Group II). Exercise load was estimated during confinement using a modified Rating of Perceived Exertion scale. Free reports were used to determine subjects' motivation. Body weight was measured before, during, and after confinement. RESULTS: Group I achieved their lowest exercise loads during their first month of isolation; problems with adaptation to the isolation environment were also reported during this first month. Group II exercise load was significantly lower in the second month due to crewmember problems; loss of motivation could be noted from their free reports. The subject with the lowest exercise load retired from the isolation experiment earlier than scheduled. Exercise load was not correlated with prior exercise habits. Significant differences in body weight was observed between group I and II and between Russian and non-Russian subjects. One subject in Group I experienced a significant increase in his body weight. CONCLUSION: Exercise load may be a good indicator for adaptation problems and motivation changes in closed environments. Immobility, lack of space, and smoking cessation in general did not induce significant body weight changes.

Exercise/physiology↗
NASA NTRS2003

Disuse exaggerates the detrimental effects of alcohol on cortical bone

BACKGROUND: Alcohol abuse is associated with an increased risk for osteoporosis. However, comorbidity factors may play an important role in the pathogenesis of alcohol-related bone fractures. Suboptimal mechanical loading of the skeleton, an established risk factor for bone loss, may occur in some alcohol abusers due to reduced physical activity, muscle atrophy, or both. The effect of alcohol consumption and reduced physical activity on bone metabolism has not been well studied. The purpose of this study was to determine whether mechanical disuse alters bone metabolism in a rat model for chronic alcohol abuse. METHODS: Alcohol was administered in the diet (35% caloric intake) of 6-month-old male rats for 4 weeks. Rats were hindlimb-unloaded the final 2 weeks of the experiment to prevent dynamic weight bearing. Afterward, cortical bone histomorphometry was evaluated at the tibia-fibula synostosis. RESULTS: At the periosteal surface of the tibial diaphysis, alcohol and hindlimb unloading independently decreased the mineralizing perimeter, mineral apposition rate, and bone formation rate. In addition, alcohol, but not hindlimb unloading, increased endocortical bone resorption. The respective detrimental effects of alcohol and hindlimb unloading to inhibit bone formation were additive; there was no interaction between the two variables. CONCLUSIONS: Reduced weight bearing accentuates the detrimental effects of alcohol on cortical bone in adult male rats by further inhibiting bone formation. This finding suggests that reduced physical activity may be a comorbidity factor for osteoporosis in alcohol abusers.

NASA Discipline Cell Biology↗
NASA NTRS2002

Solar particle event organ doses and dose equivalents for interplanetary crews: variations due to body size

Proper assessments of spacecraft shielding requirements and concomitant estimates of risk to critical body organs of spacecraft crews from energetic space radiation require accurate, quantitative methods of characterizing the compositional changes in these radiation fields as they pass through the spacecraft and overlying tissue. When estimating astronaut radiation organ doses and dose equivalents it is customary to use the Computerized Anatomical Man (CAM) model of human geometry to account for body self-shielding. Usually, the distribution for the 50th percentile man (175 cm height; 70 kg mass) is used. Most male members of the U.S. astronaut corps are taller and nearly all have heights that deviate from the 175 cm mean. In this work, estimates of critical organ doses and dose equivalents for interplanetary crews exposed to an event similar to the October 1989 solar particle event are presented for male body sizes that vary from the 5th to the 95th percentiles. Overall the results suggest that calculations of organ dose and dose equivalent may vary by as much as approximately 15% as body size is varied from the 5th to the 95th percentile in the population used to derive the CAM model data. c2002 Published by Elsevier Science Ltd on behalf of COSPAR.

NASA Discipline Radiation Health↗
NASA NTRS2002

Resting energy expenditure of rats acclimated to hypergravity

BACKGROUND: The use of centrifugation at 1 G has been advocated as a control condition during spaceflight and as a countermeasure to compensate for the adverse effects of spaceflight. Rodents are the primary animal model for the study of the effects of spaceflight and will be used in the evaluation of centrifugation as a countermeasure and means of control at 1 G during flight. HYPOTHESIS: The present study was designed to assess whether resting energy expenditure (EER) of male rats was increased in relation to the magnitude of the level of gravity to which the animals were exposed. The influence of body mass and age on resting energy expenditure (EER) of male rats (n = 42, age 40-400 d) was determined following 2 wk of acclimation to 1, 2.3, or 4.1 G. Hypergravity environments were created by centrifugation. Measurements were made at the gravity level to which the animal was acclimated and during the lights-on period. RESULTS: In rats matched for body mass (approximately 400 g), mean O2 consumption and CO2 production were higher (18% and 27%, respectively) in the 2.3- and 4.1 -G groups than controls. Mean respiratory exchange ratio (RER) increased from 0.80 to 0.87. EER was increased from 47 +/- 0.1 kcal x d(-1) at 1 G, to 57 +/- 1.5 and 58 +/- 2.2 kcal x d(-1) at 2.3 and 4.1 G, respectively. There was no difference in EER between the hypergravity groups. When age differences were considered, EER (kcal x kg(-1) x d(-1)) with increased gravity was 40% higher than at 1 G. The increase in EER was not proportional over gravity levels. CONCLUSION: Acclimation of rats to hypergravity increases their EER, dependent on body mass and age, and may alter substrate metabolism. The increase in EER was not related to the level of gravity increase.

NASA Center ARC↗
NASA NTRS1985

Activity in the ferret: oestradiol effects and circadian rhythms

The present study was conducted to determine whether oestradiol increases activity in the European ferret (Mustela furo), whether this effect is sexually dimorphic, and whether a 24-h rhythm is present in the ferret's daily activity. The activity of male and female adult, postpubertally gonadectomized ferrets was monitored while they were maintained singly on a 13:11 light-dark cycle, before and after implantation with oestradiol-17 beta. Gonadectomized male and female ferrets exhibited equal levels of activity, and neither sex exhibited a significant change in activity following oestradiol implantation. None of the ferrets exhibited a strong circadian rhythm, although weak 24-h rhythms and shorter harmonic rhythms were present. Golden hamsters (Mesocricetus auratus), monitored in an identical manner, exhibited strong circadian rhythms. It was concluded that oestradiol administration may not cause an increase in activity in the ferret, and that this species lacks a strong circadian activity rhythm.

Non-NASA Center↗
NASA NTRS1994

Acute, 2-week, and 13-week inhalation toxicity studies on dimethylethoxysilane vapor in Fischer 344 rats

Dimethylethoxysilane (DMES), a volatile liquid, is used by NASA to waterproof the heat-protective silica tiles and blankets on the Space Shuttle. Acute, 2-wk, and 13-wk inhalation exposures to DMES vapor were conducted in male and female Fischer 344 rats. In the acute study, rats were exposed to 4000, 2000, 1000, 500, or 0 (control) ppm DMES for 4 h and observed for 14 days. There were no deaths. Narcosis and ataxia were observed in rats of the two highest concentrations only. These signs disappeared within 1 h following exposure. There were no DMES-related gross or microscopic tissue lesions in rats of all exposure groups. In the 2-wk study, rats were exposed for 6 h/day, 5 days/wk to 3000, 1000, 300, 100, or 0 ppm DMES. During exposure, narcosis was observed in rats of the 3000 and 1000 ppm groups. There was a mild decrease in body weight gain in rats of the 3000 ppm group. A decrease in platelet count, an increase in bile acids, and reduced weights of the thymus, testis, and liver were observed in rats of the 3000 ppm group. Microscopically, hypospermatogenesis and spermatid giant cells were observed in the seminiferous tubules of the testes of rats exposed to 3000 ppm DMES. In the 13-wk study, rats were exposed 6 h/day, 5 days/wk to 2000, 600, 160, 40, or 0 ppm DMES. During exposure, rats of the 2000 ppm group exhibited mild narcosis and loss of startle reflex. Recovery from these central nervous system signs was rapid. Body weights were mildly decreased for rats of the 2000 ppm group. There were no exposure-related effects in hematology, serum chemistry, or urinalysis. Female rats of the 2000 ppm group had delayed estrous cycles (6 days compared to 5 days in control rats). Noteworthy organ weight changes in rats of the 2000 ppm group included decreases in thymus, liver, and testicular weights; however, pathologic lesions were observed in the testes only. Sperm motility, epididymal sperm count, and testicular spermatid count were dramatically reduced. Microscopic lesions included degeneration of the seminiferous tubular cells, pyknosis or absence of germ cells, and hypospermia in the epididymis. Rats of the 600 ppm group had a slight decrease in thymic weight and a transient decrease in body weight. Results of the acute, 2-wk, and 13-wk inhalation studies indicate DMES concentrations of 1000 ppm and higher produce narcosis that rapidly disappears following exposure. Repeated exposure of rats to DMES at either 3000 ppm for 2 wk or 2000 ppm for 13 wk caused testicular atrophy and hypospermia in male rats. Female rats exposed to 2000 ppm for 13 wk had delayed estrous cycles. Toxicological effects in rats of the 600 ppm group were minimal and equivocal. The 160 ppm concentration was a no-observable-effect level (NOEL) for 13 wk of exposure to DMES.

NASA Discipline Number 04-10↗