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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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86 records · Page 5
All sourcesNASA NTRSDOE OSTI
NASA NTRS2006

Space Exploration: A Risk for Neural Stem Cells

During spaceflights beyond low Earth orbit, astronauts are exposed to potentially carcinogenic and tissue damaging galactic cosmic rays, solar proton events, and secondary radiation that includes neutrons and recoil nuclei produced by nuclear reactions in spacecraft walls or in tissue (1). Such radiation risk may present a significant health risk for human exploration of the moon and Mars. Emerging evidence that generation of new neurons in the adult brain may be essential for learning, memory, and mood (2) and that radiation is deleterious to neurogenesis (3-5) underscores a previously unappreciated possible risk to the cognitive functions and emotional stability of astronauts exposed to radiation in space. Here we use a novel reporter mouse line to identify at-risk populations of stem and progenitor cells in the brain and find, unexpectedly, that quiescent stem-like cells (rather than their rapidly dividing progeny) in the hippocampus constitute the most vulnerable cell population. This finding raises concerns about the possible risks facing astronauts on long duration space missions.

Encinas, Juan M.↗
NASA NTRS2015

Increased Brain Activation for Foot Movement During 70-Day 6 Deg Head-Down Bed Rest (HDBR): Evidence from Functional Magnetic Resonance Imaging (fMRI)

Bed rest has been widely used as a simulation of weightlessness in studying the effects of microgravity exposure on human physiology and cognition. Changes in muscle function and functional mobility have been reported to be associated with bed rest. Understanding the effect of bed rest on neural control of movement would provide helpful information for spaceflight. In the current study, we evaluated how the brain activation for foot movement changed as a function of bed rest. Eighteen healthy men (aged 25 to 39 years) participated in this HDBR study. They remained continuously in the 6deg head‐down tilt position for 70 days. Functional MRI was acquired during 1‐Hz right foot tapping, and repeated at 7 time points: 12 days pre‐, 8 days pre‐, 7 days in‐, 50 days in‐, 70 days in‐, 8 days post‐, and 12 days post‐ HDBR. In all 7 sessions, we observed increased activation in the left motor cortex, right cerebellum and right occipital cortex during foot movement blocks compared to rest. Compared to the pre‐HDBR baseline (1st and 2nd sessions), foot movement‐induced activation in the left hippocampus increased during HDBR. This increase emerged in the 4th session, enlarged in the 5th session, and remained significant in the 6th and 7th sessions. Furthermore, increased activation relative to the baseline in left precuneus was observed in the 5th, 6th and 7th sessions. In addition, in comparison with baseline, increased activation in the left cerebellum was found in the 4th and 5th sessions, whereas increased activation in the right cerebellum was observed in the 4th, 6th and 7th sessions. No brain region exhibited decreased activation during bed rest compared to baseline. The increase of foot movement related brain activation during HDBR suggests that in a long‐term head‐down position, more neural control is needed to accomplish foot movements. This change required a couple of weeks to develop in HDBR (between 3rd and 4th sessions), and did not return to baseline even 12 days after HDBR. The observed effect of bed rest on brain activation during a foot tapping task could be linked to HDBR related changes in brain structure that we have recently reported. The relationship between pre‐ and post‐ HDBR changes in brain activation and performance in a functional mobility test will also be presented.

Yuan, P.↗
NASA NTRS2015

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

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

epigenetic developmental programming↗
NASA NTRS2017

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

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

Schorn, Julia M.↗
NASA NTRS2017

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

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

rodent development spacefligh↗
NASA NTRSDate not supplied

Human placenta-derived stromal cells mitigate select immune responses to simulated weightlessness

Space flight presents unique risks to human health. Microgravity and social isolation are important space flight stressors which have vast impact on multiple systems such as the musculoskeletal, immune and central nervous system (CNS). To explore candidate countermeasures against tissue decrements caused by spaceflight, we performed a pilot study with PLacental-eXpanded stromal (PLX) cells. PLX cells secrete factors that modulate the immune system, but do not trigger host immune responses, enabling treatment in subjects that have intact immune systems. These cells had previous success in treating critical limb ischemia and acute radiation syndrome in murine models. In this study, 4-month-old female mice underwent 30 days of hindlimb unloading (HU) in single housing conditions to simulate long-term weightlessness and isolation. HU and normally ambulating controls were administered with PLX cells or sham-injected with Plasmalyte. We hypothesized that administration of PLX cells will mitigate some of the effects caused by prolonged HU. We found that treatment with PLX cells was well tolerated as indicated by body weights, circulating corticosterone levels and immune organ response to injection of the cells. HU led to the expected decreases in soleus muscle weights and bone loss. We did not observe any protective properties of the PLX cells in the musculoskeletal system but found that the cell treatment partially protected from a subset of HU-induced immune and CNS changes. In the hippocampus, protein levels of 9 of 44 cytokines were downregulated by HU. PLX administration mitigated changes in expression of 8 of these cytokines, including IL-2, IL-6 and MCP-1. To our knowledge, this is the first report on the protective effects of PLX-PAD against HU-induced changes in the cytokine milieu of the CNS. Our findings warrant further studies, which includes testing in actual spaceflight.

Microgravity↗
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↗
DOE OSTI2025

Role of tau versus TDP-43 pathology on medial temporal lobe atrophy in aging and Alzheimer's disease

Hippocampal atrophy on magnetic resonance imaging is an important biomarker in Alzheimer's disease (AD). While hippocampal atrophy was thought to result from tau tangles in AD, different neuropathologies can lead to hippocampal atrophy, especially TAR DNA-binding protein 43 (TDP-43) pathology. In this narrative review, we evaluate existing studies on the relative contribution of tau and TDP-43 pathology to medial temporal lobe (MTL) atrophy. We report a clear association of both tau and TDP-43 neuropathology with MTL atrophy, even after correcting for other neuropathologies. Next, we discuss a potential synergism between tau and TDP-43 and the relative timing of the effects of both neuropathologies. Finally, avenues for future research will be discussed. A better understanding of the interplay between tau and TDP-43 neuropathologies and their effect on atrophy will help with the development of more specific biomarkers for limbic-predominant age-related TDP-43 encephalopathy and pinpointing of the optimal timing for testing anti-tau and anti-TDP-43 treatments in trials.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

Imaging crossing fibers in mouse, pig, monkey, and human brain using small-angle X-ray scattering

Myelinated axons (nerve fibers) efficiently transmit signals throughout the brain via action potentials. Multiple methods that are sensitive to axon orientations, from microscopy to magnetic resonance imaging, aim to reconstruct the brain's structural connectome. As billions of nerve fibers traverse the brain with various possible geometries at each point, resolving fiber crossings is necessary to generate accurate structural connectivity maps. However, doing so with specificity is a challenging task because signals originating from oriented fibers can be influenced by brain (micro)structures unrelated to myelinated axons. X-ray scattering can specifically probe myelinated axons due to the periodicity of the myelin sheath, which yields distinct peaks in the scattering pattern. Here, in this work, we show that small-angle X-ray scattering (SAXS) can be used to detect myelinated, axon-specific fiber crossings. We first demonstrate the capability using strips of human corpus callosum to create artificial double- and triple-crossing fiber geometries, and we then apply the method in mouse, pig, vervet monkey, and human brains. We compare results to polarized light imaging (3D-PLI), tracer experiments, and to outputs from diffusion MRI that sometimes fails to detect crossings. Given its specificity, capability of 3-dimensional sampling and high resolution, SAXS could serve as a ground truth for validating fiber orientations derived using diffusion MRI as well as microscopy-based methods.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2026

Acute wood smoke exposure is associated with cell-specific hippocampal transcriptomic responses in an accelerated ovarian failure mouse model

Background Wildfire events are increasing in frequency and intensity, and aging individuals demonstrate heightened biological susceptibility to air pollution exposures including increased risk of neurological sequelae. Declining ovarian hormones levels that occur with aging in females along with associated systemic physiological and inflammatory changes may contribute to increased cerebral vulnerability to air pollution, representing a potential but underexplored mechanism. Menopause and the menopausal transition represent a period of profound physiological change that affects cardiovascular, neurological, and immune health. Methods We tested whether peri-menopausal–like hormonal status amplifies hippocampal responses to acute wood smoke (WS) using an ovary-intact, 4-vinylcyclohexene diepoxide (VCD) model of moderate accelerated ovarian failure (AOF) in female C57BL/6 mice. Animals were exposed to HEPA-filtered air (FA) or WS for 4 h/day over 2 consecutive days (∼0.5 mg/m³). Exposure characterization confirmed a complex mixture of combustion products with significant levels of both trace metals and gas release during WS exposure. Results Spatial transcriptomics (10x Visium; n = 4 sections/group) with automated cell-type annotation identified astrocytes, GABAergic and glutamatergic neurons, oligodendrocytes, revealed cell type-specific transcriptional alterations following WS exposure. Distinct transcriptional patterns were observed across all identified neuronal and glial cell populations. Conclusion Together, these findings define a cell-type specific transcriptomic framework describing how WS exposure and ovarian hormone decline interact to influence hippocampal responses and identify potential cellular pathways relevant to hippocampal vulnerability.

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTAN↗
DOE OSTI2022

Natural switches in behaviour rapidly modulate hippocampal coding

Throughout their daily lives, animals and humans often switch between different behaviours. However, neuroscience research typically studies the brain while the animal is performing one behavioural task at a time, and little is known about how brain circuits represent switches between different behaviours. Here we tested this question using an ethological setting: two bats flew together in a long 135 m tunnel, and switched between navigation when flying alone (solo) and collision avoidance as they flew past each other (cross-over). Bats increased their echolocation click rate before each cross-over, indicating attention to the other bat. Hippocampal CA1 neurons represented the bat’s own position when flying alone (place coding). Notably, during cross-overs, neurons switched rapidly to jointly represent the interbat distance by self-position. This neuronal switch was very fast—as fast as 100 ms—which could be revealed owing to the very rapid natural behavioural switch. The neuronal switch correlated with the attention signal, as indexed by echolocation. Interestingly, the different place fields of the same neuron often exhibited very different tuning to interbat distance, creating a complex non-separable coding of position by distance. Theoretical analysis showed that this complex representation yields more efficient coding. Overall, our results suggest that during dynamic natural behaviour, hippocampal neurons can rapidly switch their core computation to represent the relevant behavioural variables, supporting behavioural flexibility.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2020

Scalable method for micro-CT analysis enables large scale quantitative characterization of brain lesions and implants

Anatomic evaluation is an important aspect of many studies in neuroscience; however, it often lacks information about the three-dimensional structure of the brain. Micro-CT imaging provides an excellent, nondestructive, method for the evaluation of brain structure, but current applications to neurophysiological or lesion studies require removal of the skull as well as hazardous chemicals, dehydration, or embedding, limiting their scalability and utility. Here we present a protocol using eosin in combination with bone decalcification to enhance contrast in the tissue and then employ monochromatic and propagation phase-contrast micro-CT imaging to enable the imaging of brain structure with the preservation of the surrounding skull. Instead of relying on descriptive, time-consuming, or subjective methods, we develop simple quantitative analyses to map the locations of recording electrodes and to characterize the presence and extent of hippocampal brain lesions.

3-D reconstruction↗
DOE OSTI2023

EpiPro, a Novel, Synthetic, Activity-Regulated Promoter That Targets Hyperactive Neurons in Epilepsy for Gene Therapy Applications

Epileptogenesis is characterized by intrinsic changes in neuronal firing, resulting in hyperactive neurons and the subsequent generation of seizure activity. These alterations are accompanied by changes in gene transcription networks, first with the activation of early-immediate genes and later with the long-term activation of genes involved in memory. Our objective was to engineer a promoter containing binding sites for activity-dependent transcription factors upregulated in chronic epilepsy (EpiPro) and validate it in multiple rodent models of epilepsy. First, we assessed the activity dependence of EpiPro: initial electrophysiology studies found that EpiPro-driven GFP expression was associated with increased firing rates when compared with unlabeled neurons, and the assessment of EpiPro-driven GFP expression revealed that GFP expression was increased ~150× after status epilepticus. Following this, we compared EpiPro-driven GFP expression in two rodent models of epilepsy, rat lithium/pilocarpine and mouse electrical kindling. In rodents with chronic epilepsy, GFP expression was increased in most neurons, but particularly in dentate granule cells, providing in vivo evidence to support the “breakdown of the dentate gate” hypothesis of limbic epileptogenesis. Finally, we assessed the time course of EpiPro activation and found that it was rapidly induced after seizures, with inactivation following over weeks, confirming EpiPro’s potential utility as a gene therapy driver for epilepsy.

60 APPLIED LIFE SCIENCES↗