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All sourcesNASA NTRSDOE OSTI
NASA NTRSDate not supplied

An Open-Science Approach to Address Individual Response to Simulated GCR In Genetically Diverse Populations of Mice and Humans

This project addresses the challenge of understanding and predicting individual radiation sensitivity by integrating genetics, demographics and biomarker characteristics across species (mice and humans). We hypothesize that ex vivo DNA repair response to GCR components is a central determinant of cancer risk from space radiation and can serve as a biomarker of radiation risk in combination with genetics. Automated image quantification of 53BP1+ radiation-induced foci (RIF) during the first 4-48 h post-irradiation was performed as a function of dose and LET in non-immortalized primary skin fibroblasts derived from 76 mice across 15 strains (5 inbred reference strains and 10 collaborative-cross strains) exposed to X rays (0.1, 1 and 4 Gy), 350 MeV/n 40Ar and 600 MeV/n 56Fe (1.1 and 3 particles/100sq. μm), as well as in peripheral blood mononuclear cells (PBMCs) from 768 healthy donors (matched ethnicity, 50/50 male/female, 18-70 years old) exposed to gamma rays (0.1 and 1 Gy), 350 MeV/n 28Si, 350 MeV/n 40Ar and 600 MeV/n 56Fe (1.1 and 3 particles/100sq. μm). A genome-wide association study (GWAS) was performed on the mouse strains between DNA damage responses to space radiation and single nucleotide polymorphisms (SNPs). We found SNPs, which were significantly associated to the RIF phenotype, mapped to genes and pathways that are functionally linked to health hazards for deep space exploration (e.g. carcinogenesis, nervous system damage and immune dysfunction). Some of these SNPs were located within protein coding regions, potentially interfering with protein functions and providing promising genetic targets for countermeasures. We also found correlations between both spontaneous and radiation-induced DNA damage and SNPs mapped to pathways associated with cellular metabolism. GWAS is undergoing for the human data. All data have been made available via the NASA Space Biology Open-Science database (genelab.nasa.gov) and we will discuss how various genomic and transcriptomic datasets can be accessed for modeling and integrated using machine learning methods for discovering new radiation biology.

Sylvain V Costes↗
NASA NTRSDate not supplied

Optimizing Single Nuclei Sequencing of Brain Samples From Space Flown Mice Across Age and Strain

The NASA GeneLab Sample Processing Laboratory offers high-throughput sequencing services to NASA-funded space biology researchers. Space biology studies have specific challenges such as low sample numbers, introducing susceptibility to batch effects from sample handling. These issues are compounded by complex protocols such as single-nuclei isolation and sequencing, which has recently become an attractive methodology for assessing the cellular diversity within spaceflight samples. High quality single-nuclei sequencing requires reproducible protocols to dissociate tissue and generate clean suspension of intact single nuclei. Producing single-nuclei suspension from brain tissue is particularly challenging due to cell type heterogeneity and the myelin sheath that carries over into the nuclei suspension as debris. Current procedures tend to be time consuming and sometimes include steps that can alter gene expression and create cell-type bias. Commercially available nuclei isolation kits, such as the 10X Genomics nuclei isolation kit, offers a streamlined way to process samples for nuclei isolation, thereby minimizing batch effects and enabling reproducibility. In this study, we report on the performance of the 10X Genomics nuclei isolation kit and Chromium Next GEM Single Cell Multiome ATAC + Gene Expression kit to generate sequencing libraries from space-flown mouse brain samples. Single nuclei sequencing was performed on frozen mouse brain tissue from two spaceflight missions, Rodent Research-10 (RR-10) and RR Reference Mission-2 (RRRM-2). RR-10 mice were female B6129SF2/J, euthanized at 18-19 weeks whereas RRRM-2 mice were female C57BL/6NTac, euthanized at 20 or 37 weeks. Sequencing data was processed using standard GeneLab data processing pipelines. We report evaluation of the performance of the 10X Genomics nuclei isolation kit for spaceflight samples from mouse brain, and evaluation of reproducibility across different mouse strains and age groups. We also report preliminary scientific results including cell type inference, cell clustering, and differentially expressed genes and pathways between spaceflight and ground control samples.

RR-10↗
NASA NTRSDate not supplied

Deletion of Cdkn1a in Mice Rescues Reduced Osteogenesis in Microgravity and Increases Coupled Osteoclastic Bone Degenerative Activity and Bone Loss

Elevated Cdkn1a/p21 levels in mouse bone during spaceflight have led us to hypothesize that this cell cycle inhibitor could regulate osteogenesis in response to mechanical unloading in microgravity. Cdkn1a interacts with cyclins CDK1/2/4,6 during G1 and S phases, and suppression of its expression by mechanical stretch enhances proliferation and mineralization in osteoblastic cell cultures. To test this hypothesis in a whole-organism model, we used C57BL/J6 WT/Cdkn1a-null mice in the NASA RR-10, 30-day ISS microgravity experiment. To quantify active mineralization in microgravity mice were injected with Calcein seven and two days before euthanasia on-orbit, followed by high-resolution confocal imaging of optically cleared femoral endosteal surfaces. To quantify cortical and cancellous bone parameters we conducted microCT analyses of the femur and tibia. Confocal imaging revealed a population of mineralizing calcein-positive single osteoblasts, and multicellular surfaces of mineralization by osteocytes in lacunae. The Cdkn1a-null genotype shows a greater ratio of early-osteoblasts to late-osteocytes and reduced mineralization versus WT. Additionally, in microgravity WT bones have a large (80%) decrease in active mineralization, but remarkably Cdkn1a deletion fully rescued mineralized surface loss. MicroCT shows trends for moderate spaceflight bone loss in WT femurs, and significant losses in the tibia, while Cdkn1a-null femurs showed much larger significant tissue losses, including 25% thinner trabeculae (p < 0.01),40% thinner cortical bone (p < 0.005), and 10% lower percent cortical bone area (p < 0.05). These results indicate that endogenous bone Cdkn1a plays a key role in mechanosensitive downregulation of osteoprecursor proliferation and promotes osteocytic differentiation. In microgravity however, while Cdkn1a deletion rescues mineralization, bone loss quantified by microCT is greatly increased, likely due to the molecular coupling of osteogenesis and osteoclastogenesis. This molecular mechanism opens the possibility for potential pharmacological approaches to mitigate bone loss in space simultaneously targeting Cdkn1a and osteoclast inhibition.

Eduardo A.C. Almeida↗
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 NTRS2002

Drosophila atonal fully rescues the phenotype of Math1 null mice: new functions evolve in new cellular contexts

Many genes share sequence similarity between species, but their properties often change significantly during evolution. For example, the Drosophila genes engrailed and orthodenticle and the onychophoran gene Ultrabithorax only partially substitute for their mouse or Drosophila homologs. We have been analyzing the relationship between atonal (ato) in the fruit fly and its mouse homolog, Math1. In flies, ato acts as a proneural gene that governs the development of chordotonal organs (CHOs), which serve as stretch receptors in the body wall and joints and as auditory organs in the antennae. In the fly CNS, ato is important not for specification but for axonal arborization. Math1, in contrast, is required for the specification of cells in both the CNS and the PNS. Furthermore, Math1 serves a role in the development of secretory lineage cells in the gut, a function that does not parallel any known to be served by ato. We wondered whether ato and Math1 might be more functionally homologous than they appear, so we expressed Math1 in ato mutant flies and ato in Math1 null mice. To our surprise, the two proteins are functionally interchangeable.

Non-NASA Center↗
NASA NTRS2000

TAK1 is activated in the myocardium after pressure overload and is sufficient to provoke heart failure in transgenic mice

The transforming-growth-factor-beta-activated kinase TAK1 is a member of the mitogen-activated protein kinase kinase kinase family, which couples extracellular stimuli to gene transcription. The in vivo function of TAK1 is not understood. Here, we investigated the potential involvement of TAK1 in cardiac hypertrophy. In adult mouse myocardium, TAK1 kinase activity was upregulated 7 days after aortic banding, a mechanical load that induces hypertrophy and expression of transforming growth factor beta. An activating mutation of TAK1 expressed in myocardium of transgenic mice was sufficient to produce p38 mitogen-activated protein kinase phosphorylation in vivo, cardiac hypertrophy, interstitial fibrosis, severe myocardial dysfunction, 'fetal' gene induction, apoptosis and early lethality. Thus, TAK1 activity is induced as a delayed response to mechanical stress, and can suffice to elicit myocardial hypertrophy and fulminant heart failure.

NASA Discipline Cardiopulmonary↗
NASA NTRS1999

Contractile function is unaltered in diaphragm from mice lacking calcium release channel isoform 3

Skeletal muscle expresses at least two isoforms of the calcium release channel in the sarcoplasmic reticulum (RyR1 and RyR3). Whereas the function of RyR1 is well defined, the physiological significance of RyR3 is unclear. Some authors have suggested that RyR3 participates in excitation-contraction coupling and that RyR3 may specifically confer resistance to fatigue. To test this hypothesis, we measured contractile function of diaphragm strips from adult RyR3-deficient mice (exon 2-targeted mutation) and their heterozygous and wild-type littermates. In unfatigued diaphragm, there were no differences in isometric contractile properties (twitch characteristics, force-frequency relationships, maximal force) among the three groups. Our fatigue protocol (30 Hz, 0.25 duty cycle, 37 degrees C) depressed force to 25% of the initial force; however, lack of RyR3 did not accelerate the decline in force production. The force-frequency relationship was shifted to higher frequencies and was depressed in fatigued diaphragm; lack of RyR3 did not exaggerate these changes. We therefore provide evidence that RyR3 deficiency does not alter contractile function of adult muscle before, during, or after fatigue.

Non-NASA Center↗
NASA NTRS2003

Long-term effects of low-dose proton radiation on immunity in mice: shielded vs. unshielded

BACKGROUND: Outside the protection of the terrestrial environment, astronauts on any long-term missions will unavoidably be exposed to fields of charged particle radiation dominated by protons. These fields and their biological risks are modified in complex ways by the presence of protective shielding. METHODS: To examine the long-term effects of space-like proton exposures on immune status, we treated female C57BL/6 mice with 3 or 4 Gy of 250 MeV monoenergetic protons or the complex space-like radiation field produced after 250 MeV protons are transported through 15 g x cm(-2) aluminum shielding. The animals were euthanized 122 d post-irradiation and lymphocyte phenotypes, hematological parameters, and lymphocyte blastogenesis were characterized. RESULTS: There were significant dose-dependent decreases in macrophage, CD3+/CD8+ T, NK, platelet, and red blood cell populations, as well as low hematocrit and hemoglobin levels. In contrast, dose-dependent increases in spontaneous, but not mitogen-induced, blastogenesis were noted. The differences in dose composition between pristine and shielded proton fields did not lead to significant effects in most measures, but did result in significant changes in monocyte and macrophage populations and spontaneous blastogenesis in the spleen. CONCLUSIONS: The data indicate that whole body exposure to proton radiation at doses of the order of large solar particle events or clinical treatment fractions may have long-term effects on immune system status.

NASA Discipline Radiation Health↗
NASA NTRS2002

Phosphocreatine kinetics at the onset of contractions in skeletal muscle of MM creatine kinase knockout mice

Phosphocreatine (PCr) depletion during isometric twitch stimulation at 5 Hz was measured by (31)P-NMR spectroscopy in gastrocnemius muscles of pentobarbital-anesthetized MM creatine kinase knockout (MMKO) vs. wild-type C57B (WT) mice. PCr depletion after 2 s of stimulation, estimated from the difference between spectra gated to times 200 ms and 140 s after 2-s bursts of contractions, was 2.2 +/- 0.6% of initial PCr in MMKO muscle vs. 9.7 +/- 1.6% in WT muscles (mean +/- SE, n = 7, P < 0.001). Initial PCr/ATP ratio and intracellular pH were not significantly different between groups, and there was no detectable change in intracellular pH or ATP in either group after 2 s. The initial difference in net PCr depletion was maintained during the first minute of continuous 5-Hz stimulation. However, there was no significant difference in the quasi-steady-state PCr level approached after 80 s (MMKO 36.1 +/- 3.5 vs. WT 35.5 +/- 4.4% of initial PCr; n = 5-6). A kinetic model of ATPase, creatine kinase, and adenylate kinase fluxes during stimulation was consistent with the observed PCr depletion in MMKO muscle after 2 s only if ADP-stimulated oxidative phosphorylation was included in the model. Taken together, the results suggest that cytoplasmic ADP more rapidly increases and oxidative phosphorylation is more rapidly activated at the onset of contractions in MMKO compared with WT muscles.

NASA Discipline Cell Biology↗
NASA NTRS2001

Otx1 null mutant mice show partial segregation of sensory epithelia comparable to lamprey ears

We investigated the development of inner ear innervation in Otx1 null mutants, which lack a horizontal canal, between embryonic day 12 (E12) and postnatal day 7 (P7) with DiI and immunostaining for acetylated tubulin. Comparable to control animals, horizontal crista-like fibers were found to cross over the utricle in Otx1 null mice. In mutants these fibers extend toward an area near the endolymphatic duct, not to a horizontal crista. Most Otx1 null mutants had a small patch of sensory hair cells at this position. Measurement of the area of the utricular macula suggested it to be enlarged in Otx1 null mutants. We suggest that parts of the horizontal canal crista remain incorporated in the utricular sensory epithelium in Otx1 null mutants. Other parts of the horizontal crista appear to be variably segregated to form the isolated patch of hair cells identifiable by the unique fiber trajectory as representing the horizontal canal crista. Comparison with lamprey ear innervation reveals similarities in the pattern of innervation with the dorsal macula, a sensory patch of unknown function. SEM data confirm that all foramina are less constricted in Otx1 null mutants. We propose that Otx1 is not directly involved in sensory hair cell formation of the horizontal canal but affects the segregation of the horizontal canal crista from the utricle. It also affects constriction of the two main foramina in the ear, but not their initial formation. Otx1 is thus causally related to horizontal canal morphogenesis as well as morphogenesis of these foramina.

NASA Discipline Developmental Biology↗
NASA NTRS2001

Intracranial distribution of the sympathetic system in mice: DiI tracing and immunocytochemical labeling

The intracranial distribution of the cephalic branches of the superior cervical ganglion (scg) was studied in mice using indocarbocyanine dye (DiI) anterograde tracing. Two main branches were traced from the scg. The first branch joined the nerve of the pterygoid canal (the vidian nerve), npc, from which several intracranial sympathetic branches passed to the branches of the trigeminal nerve (tgn), abducent nerve (abn), trochlear nerve (trn), and oculomotor nerve (ocn). Most of the second branch joined the abn, from which sympathetic fibers dispersed in the distal region of the trigeminal ganglion (tgg) to form a plexus close to the ganglion's branches. Branches from this plexus joined the branches of the tgn, trn, and ocn. Several minor branches arising from the second branch of the scg were also observed. One formed a sympathetic plexus around the internal carotid artery (ica); a second formed a sympathetic plexus in the proximal region of tgg, close to its root; and a third branch coursed laterally to reach the ear by passing along the greater petrosal nerve (gpn). All of the intracranial trajectories traced from scg were found to be catecholaminergic, and likely sympathetic, using tyrosine hydroxylase (TH) immunocytochemistry.

Non-NASA Center↗
NASA NTRS1998

1,25-Dihydroxyvitamin D3 inhibition of col1a1 promoter expression in calvariae from neonatal transgenic mice

We studied the effect of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) on organ cultures of transgenic mouse calvariae containing segments of the Col1a1 promoter extending to -3518, -2297, -1997, -1794, -1763, and -1719 bp upstream of the transcription start site fused to the chloramphenicol acetyltransferase (CAT) reporter gene. 1,25(OH)2D3 had a dose-dependent inhibitory effect on the expression of the -3518 bp promoter construct (ColCAT3.6), with maximal inhibition of about 50% at 10 nM. This level of inhibition was consistent with the previously observed effect on the endogenous Col1a1 gene in bone cell models. All of the shorter constructs were also inhibited by 10 nM 1,25(OH)2D3, suggesting that the sequences required for 1, 25(OH)2D3 inhibition are downstream of -1719 bp. The inhibitory effect of 1,25(OH)2D3 on transgene mRNA was maintained in the presence of the protein synthesis inhibitor cycloheximide, suggesting that the inhibitory effect on Col1a1 gene transcription does not require de novo protein synthesis. We also examined the in vivo effect of 1,25(OH)2D3 treatment of transgenic mice on ColCAT activity, and found that 48 h treatment caused a dose-dependent inhibition of CAT activity in calvariae comparable to that observed in organ cultures. In conclusion, we demonstrated that 1,25(OH)2D3 inhibits Col1A1 promoter activity in transgenic mouse calvariae, both in vivo and in vitro. The results indicate that there is a 1, 25(OH)2D3 responsive element downstream of -1719 bp. The inhibitory effect does not require new protein synthesis.

NASA Discipline Cell Biology↗
DOE OSTI2022

Molecular basis of force-pCa relation in MYL2 cardiomyopathy mice: Role of the super-relaxed state of myosin

Here, in this study, we investigated the role of the super-relaxed (SRX) state of myosin in the structure–function relationship of sarcomeres in the hearts of mouse models of cardiomyopathy-bearing mutations in the human ventricular regulatory light chain (RLC, MYL2 gene). Skinned papillary muscles from hypertrophic (HCM–D166V) and dilated (DCM–D94A) cardiomyopathy models were subjected to small-angle X-ray diffraction simultaneously with isometric force measurements to obtain the interfilament lattice spacing and equatorial intensity ratios (I 11 /I 10 ) together with the force-pCa relationship over a full range of [Ca 2+ ] and at a sarcomere length of 2.1 μm. In parallel, we studied the effect of mutations on the ATP-dependent myosin energetic states. Compared with wild-type (WT) and DCM–D94A mice, HCM–D166V significantly increased the Ca 2+ sensitivity of force and left shifted the I 11 /I 10 -pCa relationship, indicating an apparent movement of HCM–D166V cross-bridges closer to actin-containing thin filaments, thereby allowing for their premature Ca 2+ activation. The HCM–D166V model also disrupted the SRX state and promoted an SRX-to-DRX (super-relaxed to disordered relaxed) transition that correlated with an HCM-linked phenotype of hypercontractility. While this dysregulation of SRX ↔ DRX equilibrium was consistent with repositioning of myosin motors closer to the thin filaments and with increased force-pCa dependence for HCM–D166V, the DCM–D94A model favored the energy-conserving SRX state, but the structure/function–pCa data were similar to WT. Our results suggest that the mutation-induced redistribution of myosin energetic states is one of the key mechanisms contributing to the development of complex clinical phenotypes associated with human HCM–D166V and DCM–D94A mutations.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Investigating key cell types and molecules dynamics in PyMT mice model of breast cancer through a mathematical model

The most common kind of cancer among women is breast cancer. Understanding the tumor microenvironment and the interactions between individual cells and cytokines assists us in arriving at more effective treatments. Here, we develop a data-driven mathematical model to investigate the dynamics of key cell types and cytokines involved in breast cancer development. We use time-course gene expression profiles of a mouse model to estimate the relative abundance of cells and cytokines. We then employ a least-squares optimization method to evaluate the model’s parameters based on the mice data. The resulting dynamics of the cells and cytokines obtained from the optimal set of parameters exhibit a decent agreement between the data and predictions. We perform a sensitivity analysis to identify the crucial parameters of the model and then perform a local bifurcation on them. The results reveal a strong connection between adipocytes, IL6, and the cancer population, suggesting them as potential targets for therapies.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

CT584 Is Not a Protective Vaccine Antigen against Respiratory Chlamydial Challenge in Mice

Background: Chlamydia trachomatis is the most prevalent bacterial sexually transmitted pathogen in humans worldwide. Since chlamydial infection is largely asymptomatic with the potential for serious complications, a preventative vaccine is likely the most viable long-term answer to this public health threat. Cell-free protein synthesis (CFPS) utilizes the cellular protein manufacturing machinery decoupled from the requirement for maintaining cellular viability, offering the potential for flexible, rapid, and decentralized production of recombinant protein vaccine antigens. Methods: Here, we use CFPS to produce the full-length putative chlamydial type three secretion system (T3SS) needle-tip protein, CT584, for evaluation as a vaccine antigen in mouse models. High-speed atomic force microscopy (HS-AFM) (RIBM, Tsukuba, Japan) imaging and computer simulations confirm that CFPS-produced CT584 retains a native-like structure prior to immunization. Female mice were primed with CT584 adjuvanted with CpG-1826 intranasally (i.n.) or CpG-1826 + Montanide ISA 720 intramuscularly (i.m.), followed four weeks later by an i.m. boost before respiratory challenge with 10 4 inclusion forming units (IFU) of Chlamydia muridarum. Results: Immunization with CT584 generated robust antibody responses but weak cell-mediated immunity and failed to protect against i.n. challenge as demonstrated by body weight loss, increased lung weights, and the presence of high numbers of IFUs in the lungs. Conclusion: While CT584 was not a protective vaccine candidate, the speed and flexibility with which CFPS can be used to produce other potential chlamydial antigens make it an attractive technique for antigen production.

60 APPLIED LIFE SCIENCES↗
NASA NTRS2003

Partial segregation of posterior crista and saccular fibers to the nodulus and uvula of the cerebellum in mice, and its development

The projection of the posterior canal crista and saccular afferents to the cerebellum of embryonic and neonatal mice was investigated using carbocyanine dyes. Anterograde tracing from these two endorgans reveals a partial segregation of these two sets of afferents. The saccule projects predominantly to the uvula, with very minor input to the nodulus. The posterior canal projects mainly to the nodulus and, to a lesser extent, to the uvula. Retrograde tracing from the uvula and nodulus confirms this partial segregation for these two endorgans and extends it to other vestibular endorgans. Uvular injections result in many more labeled fibers in the gravistatic maculae than in the canals' cristae. In contrast, nodular injection reveals many more labeled fibers in the canal cristae than in the gravistatic maculae. This partial segregation may play a role in the information processing in these folia. Our developmental data suggest that the initial segregation at E17 coincides with the formation of the postero-lateral fissure. This embryonic segregation of the primary vestibular mossy fibers to the uvula and nodulus commences long before the maturity of their targets, the granule cells and unipolar brush cells. Thus, the segregation of the primary vestibular projection to the uvula and nodulus does not depend on cues related to the target cells. Rather, the segregation may reflect more global cerebellar patterning mechanisms involving guidance for the vestibular afferent fibers independent of the future target cells.

Non-NASA Center↗
NASA NTRS2002

The developmental segregation of posterior crista and saccular vestibular fibers in mice: a carbocyanine tracer study using confocal microscopy

The developmental segregation of gravistatic input mediated by saccular fibers and of angular acceleration input mediated by posterior crista (PC) fibers was analyzed for the first time in a developing mammal using carbocyanine dye tracing in fixed tissue. The data reveal a more extensive projection of either endorgan in 7-day-old mice (P7) than has previously been reported in adult mammals. While we confirm and extend many previous findings, we also describe a novel segregation of saccular and posterior crista fibers in the anterior half of the medial vestibular nucleus (Mv) not reported before. Our developmental analysis shows a progressive segregation of posterior crista and saccular fibers to their respective discrete projection areas between embryonic day 15 (E15) and birth (P0). Retention of overlap in young adult animals appears to reflect the early embryonic overlap found in most areas. The vestibular projection does not show a topological projection as has been described in many other sensory systems. We propose that the unique projection features of the vestibular endorgans may relate to the transformation of vestibular signals into a motor output in the three neuron reflex arc of the VOR, of which the primary vestibular projection constitutes the first leg.

NASA Discipline Developmental Biology↗
NASA NTRS2000

Antiorthostatic suspension for 14 days does not diminish the oxidative response of neutrophils in mice

The effects of long-term spaceflight on inflammatory responses have not been well-studied in either humans or animals. It is thus important to determine if the functions of immune and inflammatory cells are altered in models of spaceflight. One such animal model is antiorthostatic suspension (AOS), in which the experimental animal is subjected to a head-down tilt that mimics both the stress and the cephalad fluid shift experienced in spaceflight. A previous study reported that the peritoneal neutrophils from mice experiencing AOS generated less superoxide than unsuspended controls. We expanded on this study using several different stimuli and measuring the oxidative response of murine neutrophils in a variety of ways. These responses included the rate, lag period, and dose/response characteristics for superoxide generation, FACS analysis with dihydrodichlorofluorescein as a substrate, and a chemiluminescence response with luminol as a substrate. We also examined phagocytosis of three different microorganisms. While some effects of orthostatic suspension (attributable to the stress of the apparatus) were observed, no clear effects of AOS on oxidative function of the peritoneal neutrophils were seen.

NASA Discipline Regulatory Physiology↗