['Spaceflight Modulates Gene Expression in Astronauts']
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['Astronauts are exposed to a unique combination of stressors during spaceflight, which leads to alterations in their physiology and potentially increases their susceptibility to infectious pathogens. Here we report the first microarray evaluation of any astronaut tissue sample, specifically whole blood, before and after spaceflight using an array comprising 234 well-characterized stress response genes. Differentially regulated genes included those important for DNA repair, oxidative stress, and protein folding/degradation. Microarrays comprising 234 well characterized stress-related genes were used to profile transcriptomic changes in six astronauts before and after short-duration spaceflight. Blood samples were collected for analysis from each eastronaut 10 days prior and 2-3 hours after return from spaceflight. Data submitted for platform GPL140 contain genes that have been pre-filtered by the analytical software to remove values of low certainty, resulting in missing values for some samples. Unfortunately, these original data are no longer available due to physical damage at Tulane University during hurricane Katrina, but the processed values were retained in redundant locations and these are submitted for upload to GEO.']
Combined space stressors induce independent behavioral deficits predicted by early peripheral blood monocytes (Behavioral Assays)
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Interplanetary space travel poses many hazards to the human body. To protect astronaut health and performance on critical missions, there is first a need to understand the effects of deep space hazards, including ionizing radiation, confinement, and altered gravity. Previous studies of rodents exposed to a single such stressor document significant deficits, but our study is the first to investigate possible cumulative and synergistic impacts of simultaneous ionizing radiation, confinement, and altered gravity on behavior and cognition. Our cohort was divided between 6‐month‐old female and male mice in group, social isolation, or hindlimb unloading housing, exposed to 0 or 50 cGy of 5 ion simplified simulated galactic cosmic radiation (GCRsim). We report interactions and independent effects of GCRsim exposure and housing conditions on behavioral and cognitive performance. Exposure to GCRsim drove changes in immune cell populations in peripheral blood collected early after irradiation, while housing conditions drove changes in blood collected at a later point. Female mice were largely resilient to deficits observed in male mice. Finally, we used principal component analysis to represent total deficits as principal component scores, which were predicted by general linear models using GCR exposure, housing condition, and early blood biomarkers. This dataset derives results from the behavior assays Balance Beam, Elevated Plus Maze, Open Field, Three Chamber Social Approach, Novel Object Recognition, and Radial Arm Water Maze using the same source animals as the flow cytometry blood samples in OSD-640.
Combined space stressors induce independent behavioral deficits predicted by early peripheral blood monocytes (flow cytometry)
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Interplanetary space travel poses many hazards to the human body. To protect astronaut health and performance on critical missions, there is first a need to understand the effects of deep space hazards, including ionizing radiation, confinement, and altered gravity. Previous studies of rodents exposed to a single such stressor document significant deficits, but our study is the first to investigate possible cumulative and synergistic impacts of simultaneous ionizing radiation, confinement, and altered gravity on behavior and cognition. Our cohort was divided between 6‐month‐old female and male mice in group, social isolation, or hindlimb unloading housing, exposed to 0 or 50 cGy of 5 ion simplified simulated galactic cosmic radiation (GCRsim). We report interactions and independent effects of GCRsim exposure and housing conditions on behavioral and cognitive performance. Exposure to GCRsim drove changes in immune cell populations in peripheral blood collected early after irradiation, while housing conditions drove changes in blood collected at a later point. Female mice were largely resilient to deficits observed in male mice. Finally, we used principal component analysis to represent total deficits as principal component scores, which were predicted by general linear models using GCR exposure, housing condition, and early blood biomarkers. This dataset derives results from the flow cytometry assay using blood samples from same source animals used for behavioral studies in OSD-618.
Gene expression profiling for spaceflight induced-neuroinflammation in the mouse brain
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The health risk from spaceflight-induced neuronal damage and potential adverse neurovascular effects is a chief concern. More recently, it has been proposed that neuroinflammatory response plays an important role in the neurovascular remodeling in the brain after stress. The goal of the present study was to characterize changes in the gene expression of neuroinflammation panel for inflammation, neuronal function, metabolism and stress in mouse brain tissue. Ten-week old male C57BL/6 mice were launched to the International Space Station (ISS) on Space-X 12 for a 35-day mission. Within 38+4 hours of splashdown, mice were returned to Earth alive. Brain tissues were collected for analysis. Habitat ground control (GC) mice were maintained on Earth in flight hardware cages. A novel digital color-coded barcode counting technology (NanoStringTM) was used to evaluate gene expression profiles in the spaceflight mouse brain. The Neuroinflammation panel includes 757 genes covering the core pathways and processes that define neuroimmune interactions. A set of 54 differently expressed genes (p less than 0.05) significantly segregates the GC group from flight (FLT) group. Many pathways associated with cellular stress, inflammation, apoptosis, and metabolism were significantly altered by flight conditions. Genes supporting neuronal synaptic signaling and migration were significantly downregulated in FLT compared to the GC mice. A decrease in the expression of genes important for oligodendrocyte differentiation and myelin sheath maintenance was observed. Moreover, mRNA expression of many genes related to antiviral signaling, reactive oxygen species (ROS) generation, and bacterial immune response were significantly downregulated. These data indicate that neuroinflammation and altered immune reactions may be closely associate with spaceflight-induced stress response and have an impact on the neuronal function that may result in chronic neuroinflammation and late neurodegeneration. A total of 12 frozen right caudal half hemispheres containing mid- and hindbrain from GC and FLT mice (n equals 6 per group), were used for analysis
Spaceflight-Induced Gene Expression Profiles in the Mouse Brain Are Attenuated by Treatment with the Antioxidant BuOE - Cornu Ammonis 1
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The demands of deep space pose a health risk to the central nervous system that has long been a concern when sending humans to space. While little is known about how spaceflight affects transcription spatially in the brain, a greater understanding of this process has the potential to aid strategies that mitigate the effects of spaceflight on the brain. Therefore, we performed GeoMx Digital Spatial Profiling of mouse brains subjected to either spaceflight or grounded controls. Four brain regions were selected: Cortex, Frontal Cortex, Corunu Ammonis I, and Dentate Gyrus. Antioxidants have emerged as a potential means of attenuating the effects of spaceflight, so we treated a subset of the mice with a superoxide dismutase mimic, MnTnBuOE-2-PyP 5+ (BuOE). Our analysis revealed hundreds of differentially expressed genes due to spaceflight in each of the four brain regions. Both common and region-specific transcriptomic responses were observed. Metabolic pathways and pathways sensitive to oxidative stress were enriched in the four brain regions due to spaceflight. These findings enhance our understanding of brain regional variation in susceptibility to spaceflight conditions. BuOE reduced the transcriptomic effects of spaceflight at a large number of genes, suggesting that this compound may attenuate oxidative stress-induced brain damage caused by the spaceflight environment. This study contains data of cornu ammonis 1 region. The data of other brain regions are deposited in OSD-685 (dentate gyrus), OSD-698 (frontal cortex), and OSD-699 (cerebral cortex).