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At least 379 records · Page 21

Comparison of HIPWAC and Mars Express SPICAM Observations of Ozone on Mars 2006-2008 and Variation from 1993 IRHS Observations

Ozone is a tracer of photochemistry in the atmosphere of Mars and an observable used to test predictions of photochemical models. We present a comparison of retrieved ozone abundances on Mars using ground-based infrared heterodyne measurements by NASA Goddard Space Flight Center's Heterodyne Instrument for Planetary Wind And Composition (HIPWAC) and space-based Mars Express Spectroscopy for the Investigation of the Characteristics of the Atmosphere of Mars (SPICAM) ultraviolet measurements. Ozone retrievals from simultaneous measurements in February 2008 were very consistent (0.8 microns-atm), as were measurements made close in time (ranging from less than 1 to greater than 8 microns-atm) during this period and during opportunities in October 2006 and February 2007. The consistency of retrievals from the two different observational techniques supports combining the measurements for testing photochemistry-coupled general circulation models and for investigating variability over the long-term between spacecraft missions. Quantitative comparison with ground-based measurements by NASA'GSFC's Infrared Heterodyne Spectrometer (IRHS) in 1993 reveals 2-4 times more ozone at low latitudes than in 2008 at the same season, and such variability was not evident over the shorter period of the Mars Express mission. This variability may be due to cloud activity.

Fast, Kelly E.↗

MESSENGER and Venus Express Observations of the Solar Wind Interaction with Venus

At 23:08 UTC on 5 June 2007 the MESSENGER spacecraft reached its closest approach altitude of 338 kin during its final flyby of Venus en route to its 2011 orbit insertion at Mercury. The availability of the simultaneous Venus Express solar wind and interplanetary magnetic field measurements provides a rare opportunity to examine the influence of upstream conditions on this planet's solar wind interaction. We present MESSENGER observations of new features of the Venus - solar wind interaction including hot flow anomalies upstream of the bow shock, a flux rope in the near-tail and a two-point determination of the timescale for magnetic flux transport through this induced magnetosphere. Citation: Stavin, J. A., et al. (2009), MESSENGER and Venus Express observations of the solar wind interaction with Venus,

Slavin, James A.↗

Changes in Liver Metabolic Gene Expression from Radiation Exposure

Radiation exposure is one of the unique physiological challenges of human spaceflight that is not encountered on earth. While radiation exposure is known to impart physiological stresses and alter normal function, it is unclear how it specifically affects drug metabolism. A major concern is that the actions of medications used in spaceflight may deviate from the expectations formed from terrestrial use. This concern was investigated at the molecular level by analyzing how gamma radiation exposure affected gene expression in the livers of mice. Three different doses of radiation were administered and after various intervals of recovery time, gene expression was measured with RT-qPCR screening arrays for drug metabolism and DNA repair. After examining the results of 192 genes total from each of 72 mice, 65 genes were found to be significantly affected by at least one of the doses of radiation. In general, the genes affected are involved in the metabolism of drugs with lipid or steroid hormone-like structures, as well as the maintenance of redox homeostasis and repair of DNA damage.

Peters, C. P.↗

Mars Express Forward Link Capabilities for the Mars Relay Operations Service (MaROS)

This software provides a new capability for landed Mars assets to perform forward link relay through the Mars Express (MEX) European Union orbital spacecraft. It solves the problem of standardizing the relay interface between lander missions and MEX. The Mars Operations Relay Service (MaROS) is intended as a central point for relay planning and post-pass analysis for all Mars landed and orbital assets. Through the first two phases of implementation, MaROS supports relay coordination through the Odyssey orbiter and the Mars Reconnaissance Orbiter (MRO). With this new software, MaROS now fully integrates the Mars Express spacecraft into the relay picture. This new software generates and manages a new set of file formats that allows for relay request to MEX for forward and return link relay, including the parameters specific to MEX. Existing MEX relay planning interactions were performed via email exchanges and point-to-point file transfers. By integrating MEX into MaROS, all transactions are managed by a centralized service for tracking and analysis. Additionally, all lander missions have a single, shared interface with MEX and do not have to integrate on a mission-by mission basis. Relay is a critical element of Mars lander data management. Landed assets depend largely upon orbital relay for data delivery, which can be impacted by the availability and health of each orbiter in the network. At any time, an issue may occur to prevent relay. For this reason, it is imperative that all possible orbital assets be integrated into the overall relay picture.

Allard, Daniel A.↗

Chronic Lunar Dust Exposure on Rat Cornea: Evaluation by Gene Expression Profiling

Lunar dust is capable of entering habitats and vehicle compartments by sticking to spacesuits or other objects that are transferred into the spacecraft from the lunar surface and has been reported to cause irritation upon exposure. During the Apollo missions, crewmembers reported irritation specifically to the skin and eyes after contamination of the lunar and service modules. It has since been hypothesized that ocular irritation and abrasion might occur as a result of such exposure, impairing crew vision. Recent work has shown that both ultrafine and unground lunar dust exhibited minimal irritancy of the ocular surface (i.e., cornea); however, the assessment of the severity of ocular damage resulting from contact of lunar dust particles to the cornea has focused only on macroscopic signs of mechanical irritancy and cytotoxicity. Given the chemical reactive properties of lunar dust, exposure of the cornea may contribute to detrimental effects at the molecular level including but not limited to oxidative damage. Additionally, low level chronic exposures may confound any results obtained in previous acute studies. We report here preliminary results from a tissue sharing effort using 10‐week‐old Fischer 344 male rats chronically exposed to filtered air or jet milled lunar dust collected during Apollo 14 using a Jaeger‐NYU nose‐only chamber for a total of 120 hours (6 hours daily, 5 days a week) over a 4‐week period. RNA was isolated from corneas collected from rats at 1 day and 7 days after being exposed to concentrations of 0, 20, and 60 mg/m3 of lunar dust. Microarray analysis was performed using the Affymetrix GeneChip Rat Genome 230 2.0 Array with Affymetrix Expression Console and Transcriptome Analysis Console used for normalization and secondary analysis. An Ingenuity iReport"TM" was then generated for canonical pathway identification. The number of differentially expressed genes identified increases with dose compared to controls suggesting a more severe response to the lunar dust insult at higher levels. Pathways of interests that have been identified in all exposed samples include oxidative stress response, mitochondrial dysfunction, fibrosis, epithelial healing, TGF-Beta signaling, and extracellular matrix remodeling. Several biological processes related to cell migration, cellular proliferation, and eye development were also identified to be altered by exposure to lunar dust. Our preliminary results suggest that even a chronic insult of lunar dust as low as 20 mg/m(exp 3) elicits a molecular response in cornea tissue. Lunar dust on the surface of the moon would have the added properties of ionization and activation potentially leading to further damage to the cornea and greater sensitivity to any other environmental insult such as exposure to radiation. Additional studies are required to fully assess the risk of vision impairment and the mechanistic responses initiated in cornea exposed to lunar dust as well as the potential for long‐term effects to astronaut health

Theriot, C. A.↗

Persistent Expression Changes of Fibrosis Related Genes in the Lung Tissues of Rats Exposed to Lunar Dust Particles

The Moon's surface is covered by a layer of reactive dust, containing 1-2% of respirable fine dust (< 3 microns). The habitable area of any lunar landing vehicle would inevitably be contaminated with lunar dust that could pose a health risk. The purpose of the study is to evaluate the toxicity of Apollo moon dust in rodents through inhalation to assess the health risk of dust exposures to humans and to identify the mechanisms and potential pathways involved in lunar dust-induced toxicity. Ccl3, Ccl12, Cxcl2, Cxcl5, Itgb8, Tnf, Ldhc, Clec4e, Bmp7, and Smad6, showed persistently significant expression changes in the lung tissue. The expression of several of these genes were dose- and time- dependent, and were significantly correlated with other pathological. Our previous data showed that no pathological changes were detected in low dose groups. However, several genes, primarily produced by lung epithelial, were significantly altered persistently in response to low-dose dust exposure. The data presented in this study, for the first time, explores the molecular mechanisms of lunar dust induced toxicity, contributing not only the risk assessment for future space exploration, but also understandings of the dust-induced toxicity to humans on earth.

Zhang, Ye↗

Comparison of Forced ENSO-Like Hydrological Expressions in Simulations of the Preindustrial and Mid-Holocene

Using the water isotope- and vapor source distribution (VSD) tracer-enabled Goddard Institute for Space Studies ModelE-R, we examine changing El Nino-Southern Oscillation (ENSO)-like expressions in the hydrological cycle in a suite of model experiments. We apply strong surface temperature anomalies associated with composite observed El Nino and La Nina events as surface boundary conditions to preindustrial and mid-Holocene model experiments in order to investigate ENSO-like expressions in the hydrological cycle under varying boundary conditions. We find distinct simulated hydrological anomalies associated with El Nino-like ("ENSOWARM") and La Nina-like ("ENSOCOOL") conditions, and the region-specific VSD tracers show hydrological differences across the Pacific basin between El Nino-like and La Nina-like events. The application of ENSOCOOL forcings does not produce climatological anomalies that represent the equal but opposite impacts of the ENSOWARM experiment, as the isotopic anomalies associated with ENSOWARM conditions are generally stronger than with ENSOCOOL and the spatial patterns of change distinct. Also, when the same ENSO-like surface temperature anomalies are imposed on the mid-Holocene, the hydrological response is muted, relative to the preindustrial. Mid-Holocene changes in moisture sources to the analyzed regions across the Pacific reveal potentially complex relationships between ENSO-like conditions and boundary conditions. Given the complex impacts of ENSO-like conditions on various aspects of the hydrological cycle, we suggest that proxy record insights into paleo-ENSO variability are most likely to be robust when synthesized from a network of many spatially diverse archives, which can account for the potential nonstationarity of ENSO teleconnections under different boundary conditions.

boundary conditions↗

Automated and Adaptive Mission Planning for Orbital Express

The Orbital Express space mission was a Defense Advanced Research Projects Agency (DARPA) lead demonstration of on-orbit satellite servicing scenarios, autonomous rendezvous, fluid transfers of hydrazine propellant, and robotic arm transfers of Orbital Replacement Unit (ORU) components. Boeing's Autonomous Space Transport Robotic Operations (ASTRO) vehicle provided the servicing to the Ball Aerospace's Next Generation Serviceable Satellite (NextSat) client. For communication opportunities, operations used the high-bandwidth ground-based Air Force Satellite Control Network (AFSCN) along with the relatively low-bandwidth GEO-Synchronous space-borne Tracking and Data Relay Satellite System (TDRSS) network. Mission operations were conducted out of the RDT&E Support Complex (RSC) at the Kirtland Air Force Base in New Mexico. All mission objectives were met successfully: The first of several autonomous rendezvous was demonstrated on May 5, 2007; autonomous free-flyer capture was demonstrated on June 22, 2007; the fluid and ORU transfers throughout the mission were successful. Planning operations for the mission were conducted by a team of personnel including Flight Directors, who were responsible for verifying the steps and contacts within the procedures, the Rendezvous Planners who would compute the locations and visibilities of the spacecraft, the Scenario Resource Planners (SRPs), who were concerned with assignment of communications windows, monitoring of resources, and sending commands to the ASTRO spacecraft, and the Mission planners who would interface with the real-time operations environment, process planning products and coordinate activities with the SRP. The SRP position was staffed by JPL personnel who used the Automated Scheduling and Planning ENvironment (ASPEN) to model and enforce mission and satellite constraints. The lifecycle of a plan began three weeks outside its execution on-board. During the planning timeframe, many aspects could change the plan, causing the need for re-planning. These variable factors, ranging from shifting contact times to ground-station closures and required maintenance times, are discussed along with the flexibility of the ASPEN tool to accommodate changes to procedures and the daily or long-range plan, which contributed to the success of the mission. This paper will present an introduction to ASPEN, a more in-depth discussion on its use on the Orbital Express mission, and other relative work. A description of ground operations after the SRP deliveries were made is included, and we briefly discuss lessons learned from the planning perspective and future work.

scheduling↗

Column Number Density Expressions Through M = 0 and M = 1 Point Source Plumes Along Any Straight Path

Analytical expressions for column number density (CND) are developed for optical line of sight paths through a variety of steady free molecule point source models including directionally-constrained effusion (Mach number M = 0) and flow from a sonic orifice (M = 1). Sonic orifice solutions are approximate, developed using a fair simulacrum fitted to the free molecule solution. Expressions are also developed for a spherically-symmetric thermal expansion (M = 0). CND solutions are found for the most general paths relative to these sources and briefly explored. It is determined that the maximum CND from a distant location through directed effusion and sonic orifice cases occurs along the path parallel to the source plane that intersects the plume axis. For the effusive case this value is exactly twice the CND found along the ray originating from that point of intersection and extending to infinity along the plume's axis. For sonic plumes this ratio is reduced to about 4/3. For high Mach number cases the maximum CND will be found along the axial centerline path. Keywords: column number density, plume flows, outgassing, free molecule flow.

Venting↗

Column Number Density Expressions Through M = 0 and M = 1 Point Source Plumes Along Any Straight Path

Analytical expressions for column number density (CND) are developed for optical line of sight paths through a variety of steady free molecule point source models including directionally-constrained effusion (Mach number M = 0) and flow from a sonic orifice (M 1). Sonic orifice solutions are approximate, developed using a fair simulacrum fitted to the free molecule solution. Expressions are also developed for a spherically-symmetric thermal expansion (M = 0). CND solutions are found for the most general paths relative to these sources and briefly explored. It is determined that the maximum CND from a distant location through directed effusion and sonic orifice cases occurs along the path parallel to the source plane that intersects the plume axis. For the effusive case this value is exactly twice the CND found along the ray originating from that point of intersection and extending to infinity along the plumes axis. For sonic plumes this ratio is reduced to about 43. For high Mach number cases the maximum CND will be found along the axial centerline path.

Column Density↗

Column Number Density Expressions Through M = 0 and M = 1 Point Source Plumes Along Any Straight Path

Providers of payloads carried aboard the International Space Station must conduct analyses to demonstrate that any planned gaseous venting events generate no more than a certain level of material that may interfere with optical measurements from other experiments or payloads located nearby. This requirement is expressed in terms of a maximum column number density (CND). Depending on the level of rarefaction, such venting may be characterized by effusion for low flow rates, or by a sonic distribution at higher levels. Since the relative locations of other sensitive payloads are often unknown because they may refer to future projects, this requirement becomes a search for the maximum CND along any path.In another application, certain astronomical observations make use of CND to estimate light attenuation from a distant star through gaseous plumes, such as the Fermi Bubbles emanating from the vicinity of the black hole at the center of our Milky Way galaxy, in order to infer the amount of material being expelled via those plumes.This paper presents analytical CND expressions developed for general straight paths based upon a free molecule point source model for steady effusive flow and for a distribution fitted to model flows from a sonic orifice. Among other things, in this Mach number range it is demonstrated that the maximum CND from a distant location occurs along the path parallel to the source plane that intersects the plume axis. For effusive flows this value is exactly twice the CND found along the ray originating from that point of intersection and extending to infinity along the plumes axis. For sonic plumes this ratio is reduced to about 43.

Venting↗

Successful Validation of RNA Purification and Quantitative Real-Time PCR Analysis of Gene Expression on the International Space Station

The NASA Ames WetLab-2 system was developed to offer new on-orbit gene expression analysis capabilities to ISS researchers and can be used to conduct on-orbit RNA isolation and quantitative real time PCR (RT-qPCR) analysis of gene expression from a wide range of biological samples ranging from microbes to mammalian tissues. On orbit validation included three quantitative PCR (qPCR) runs using an E. coli genomic DNA template pre-loaded at three different concentrations. The flight Ct values for the DNA standards showed no statistically significant differences relative to ground controls although there was increased noise in Ct curves, likely due to microgravity-related bubble retention in the optical windows. RNA was successfully purified from both E. coli and mouse liver samples and successfully generated singleplex, duplex and triplex data although with higher standard deviations than ground controls, also likely due to bubbles. Using volunteer science activities, a potential bubble reduction strategy was tested and resulted in smooth amplification curves and tighter Cts between replicates. The WetLab-2 validation experiment demonstrates a novel molecular biology workbench on ISS which allows scientists to purify and stabilize RNA, and to conduct RT-qPCR analyses on-orbit with rapid results. This novel ability is an important step towards utilizing ISS as a National Laboratory facility with the capability to conduct and adjust science experiments in real time without sample return, and opens new possibilities for rapid medical diagnostics and biological environmental monitoring on ISS.

microgravity↗

Informing Rodent Behavior in Space: Gene Expression and Hyper-Emotionality Following Prenatal Stress

As space exploration pushes our boundaries further away from Earth and for longer durations, we will inevitably require the use of multi-generational studies to continue our expansion. Space is a stressful environment not only due to the deleterious effect of spaceflight on physiology, but also due to confinement, limited social interactions, inherently dangerous circumstances, and many other stresses of an unknown environment. Stress can alter the brain chemistry, and these alterations can affect behavior at all stages of development, but it is especially pronounced during the perinatal period and can have longstanding effects, even into adulthood, which manifest through augmented brain function and psychopathology. This study investigated the nexus of brain chemistry and brain function by observing behavior of adult rats whose mothers were exposed to unpredictable variable prenatal stress (UVPS) while they were in the womb. The UVPS consisted of strobe light, tube restraint, and white noise, and was administered at unpredictable times of the day and also varied in length, both of which were measures taken to prevent habituation to the stressor. The offspring rats were then allowed to reach adulthood and at 90 days were subjected to a series of behavioral tests including novel object, startle response, and an unknown intruder to quantify the adult rats stress response and anxiety. Here we report these results of the behavioral analysis and correlate adult behavioral measures with the expression of genes involved in the hypothalamic-pituitary-adrenal axis, which modulates the animals stress response. We hypothesized that hyper-expression of genes involved in the HPA axis would correlate with the observed anxiety-like behaviors associated with early stress.

Moyer, E. L.↗

Increasing the Statistical Rigor of Cross-Species Differential Expression Analysis

Microgravity inflicts substantial, but undercharacterized, pressure on organisms that induces metabolic responses such as increased microbial virulence and antibiotic resistance, altered organ weights in developing rats, and loss of bone tissue in astronauts. Numerous studies have analyzed the effects of microgravity on specific organisms, tissues, or test conditions, but these projects are necessarily limited by the small sample size of space research. Increasing the sample size of spaceflight studies is non-trivial; however, pooling data from numerous studies can greatly increase the statistical rigor of comparative analyses. The GeneLab houses datasets from 73 spaceflight studies that performed transcription profiling assays. These data encompass a diverse array of organisms ranging from Escherichia coli to Mus musculus to Homo sapiens and comprise studies analyzing ionizing radiation, mammalian pregnancy, etc. Collectively, the GeneLab database contains a large quantity of transcription assays and RNA sequence data analyzing Differential Gene Expression (DGE) between microand normogravity. Xspecies, a cross-species analysis method for DGE developed by Kristiansson, et al. in 2012, identifies homologous genes between species that are universally up- or downregulated in response to test conditions. Previous work by an intern at GeneLab applied Xspecies to 19 datasets containing seven different species and identified 14 homologous groups differentially expressed under spaceflight conditions including several heat shock proteins and cytoskeletal components. Unfortunately, these results may be biased by the disproportionate number of studies on Arabidopsis thaliana (5) and Mus musculus (6) and the results are not normalized by evolutionary distances. Here, we present modifications to the Xspecies algorithm that permits incorporation of multi-omic data and normalizes data for effect size, directionality, and evolutionary distances. We then apply this algorithm to all currently available GeneLab studies

Xspecies↗

Gene Expression of Pathogens in Simulated Microgravity

Extended exposure to radiation and microgravity in space has been linked to astronauts developing chronic diseases upon returning to Earth. The Gram-negative pathogen Serratia marcescens has been shown to potentially cause significant infections in humans and in insect models on Earth. Our recent findings also showed that S. marcescens shows an increase in virulence after a short period of growth in the spaceflight environment, which raises initiatives to find the correlation between space environment and the increased virulence. Because we know that the health of astronauts is immunocompromised in space, it is possible that the combination of increased bacterial virulence and the weakened immune system will cause astronauts to be more susceptible to chronic diseases in extended spaceflight. With 75% of human disease genes being conserved in the fruit fly Drosophila melanogaster, these insects act as an ideal model organism to study the human immune system. The high accessibility, low cost, high rate of reproductivity, and short lifespans of D. melanogaster facilitate efficient, high-quality research that seeks to understand altered virulence of this opportunistic pathogen. In this ground-based study, we will use a rotating wall vessel apparatus to simulate microgravity and determine how pathogenicity changes by evaluating differences in gene expression for S. marcescens between bacteria grown in simulated microgravity conditions and controls. We will compare the results of our findings to gene expression patterns in actual spaceflight samples of S. marcescens grown on the ISS (International Space Station) during a recent validation mission, to see if there are common mechanisms across our simulated microgravity and actual spaceflight microgravity samples that both show increased virulence in the fruit fly. With extended space travel in the foreseeable future, understanding how human physiology will be affected by these different factors will help mitigate risks and deaths.

spaceflight analogue↗

Prenatal 2g Exposure Alters Placental Expression of Stress-Related Genes

Extra-terrestrial colonization is of growing interest to space agencies and private entities, emphasizing the importance of research on reproduction and development in the absence of Earth's 1G. Maternal stressors can modify offspring development, exerting significant lifespan and crossgenerational changes through prenatal programming. The space environment is stressful, therefore exposure to altered gravity during pregnancy may impact later life outcomes in offspring. In ground-based studies, we exposed pregnant rats to continuous +G (above Earth gravity), and observed overweight and elevated anxiety in adult male (but not female) offspring, common phenotypes associated with prenatal maternal stress. Here we hypothesize that exposure to increased gravity during pregnancy elicits changes in the expression of stress-related genes in placenta that may mediate emergence of later life outcomes. While the placenta transports maternal factors to the fetus and produces endogenous fetal hormones, stress-induced changes at the placental-uterine interface may also alter communication between mother and fetus, facilitating prenatal transmission of unfavorable later life outcomes and cross-generational epigenetic alterations. Maternal stress elevates maternal glucocorticoids however placental 11b-hydroxysteroid dehydrogenase type 2 (HSD11B2) buffers fetal exposure by converting cortisol/corticosterone into inactive metabolites. Maternal stress during pregnancy down-regulates this enzyme and can induce epigenetic changes in placental and fetal tissues accounting for heightened adult HPA reactivity. Past studies have shown a placenta-specific increase in DNA methyltransferase (DNMT3a) mRNA in stressed mothers, an effect with implications for genome-wide epigenetic changes that may account for diverse phenotypic outcomes following maternal stress. Here we exposed groups of pregnant rats to one of five gravity loads (1, 1.5, 1.75 and 2G) and analyzed placental samples during late gestation. We predicted a systematic dose-response relationship between gravity load and the expression of the HSD11B2 and DNMT3 genes, thereby linking maternal exposure to altered gravity during pregancy with maternal stress.

Kalotia, Simranjit K.↗

Simulated Microgravity Affects Behavior and Cytokine Expression in the Hippocampus of Adult Mice: Influence of Mitochondrial Reactive Oxygen Species

The effects of microgravity, and social isolation on the CNS are poorly understood. We hypothesize that mitochondrial reactive oxygen species (ROS) play an important role in this process. Since mice are social animals, our lab developed a novel social model of hindlimb unloading (HU), enabling us to determine the effects of both social isolation and simulated microgravity. Responses to 30d of HU were compared in wildtype or transgenic MCAT mice who over-express human catalase in mitochondria. Abundance of 4-Hydroxynonenal, Park7 (a redox-sensitive chaperone and sensor of oxidative stress) and corticosterone were measured by ELISA. Cytokines related to inflammation in the hippocampus and in plasma were analyzed by a protein array. Behavioral data was collected over a 24-hour period.Socially housed HU mice were more active and conducted at least two times more exploratory activities, compared to normally loaded mice. Correlation analysis revealed that specific brain and plasma cytokines correspond with specific behaviors. Simulated microgravity and/or social isolation caused changes in cytokine patterns in the hippocampus and in plasma, with significant interaction effects of HU and genotype in expression levels of five cytokines (out of 35). Interestingly, elevation of these generally pro-inflammatory cytokines by HU in WT mice was mitigated in MCAT mice, suggesting a role for mitochondrial ROS signaling in inflammatory CNS responses to microgravity. Interestingly, socially housed mice had also lower level of 4HNE and higher level of Park7 in the hippocampus compared to singly housed animals. The cytokine responses to social isolation were more extensive in brain vs plasma. Further, there was no overlap in the cytokine repertoire regulated in response to microgravity versus, isolation suggesting divergent mechanisms or downstream signaling. These findings implicate a potentially important role for mitochondrial ROS in CNS responses to the challenges posed both by prolonged missions in space and bedrest on Earth

Guttmann, Linda↗

A Gene Expression and Histologic Approach to Study Production and Outflow of Cerebrospinal Fluid in Hindlimb Suspended Rats

INTRODUCTION: The Spaceflight Associated Neuro-ocular Syndrome (SANS) is thought to be associated with weightlessness-induced cephalad fluid shift, possibly associated with a chronic elevation of intracranial pressure (ICP) during long-duration ISS missions. Changes in cerebrospinal fluid (CSF) dynamics and cranial compliance might be involved in the ICP increase. It is not known whether CSF production and/or outflow are altered in microgravity, but changes at the molecular and cellular level in the structures that produce and regulate the transcellular and paracellular secretion and reabsorption of CSF may be relevant. In this study, we used the rat hindlimb suspension (HS) model to examine the relationship between intracranial pressure (ICP) and the cellular responses to the prolonged change in body posture elicited specifically in the choroid plexus (CP). This was evaluated by transcriptomics, histopathology and ultrastructure of the CP and arachnoid villi (AV). METHODS: ICP was measured by telemetry. The morphology, ultrastructure, and gene expression profile of the CP was examined using male 9-month-old Long Evans rats subjected to HS for 14 and 90 days. A subset of animals completing 90-day HS returned to normal posture for 14 and 90 additional days of recovery. All HS rats had age-matched cage controls maintained in normal posture. A group of animals was maintained in conditions of 1% CO2 throughout the entire protocol. The rat brains were carefully removed and preserved for various analyses, including transmission electron microscopy (TEM), immunohistochemical analysis of specific targets involved in CSF regulation, and RNA sequencing analysis of laser capture micro-dissected CP tissue from the lateral ventricles. SUMMARY OF RESULTS: The ICP record was limited, which impacted any conclusions derived from the results. However, the ICP of rats in the CO2-enriched atmosphere appeared increased compared to those in a normal air composition. HS of rats resulted in an altered transcriptomics profile in the choroid plexus compared to animals maintained at normal posture. This was observed during both the HS period and during normal posture recovery period following 90 days of suspension. The greatest number of differentially expressed genes was observed at 90 days HS. Elevated CO2 also led to a different transcriptomics profile in the CP. The histology and ultrastructure results should be considered preliminary due to the limited number of samples. Examination of the CP by TEM showed blood vessel congestion and microvilli swelling in the CP, as well as some subpial and periventricular gliosis, but no associations were observed with treatment. There was no evidence of a reduced clearance of b-amyloid in the periventricular, perivascular and subpial regions of the brain in HS animals versus those in normal posture. Immunohistochemical staining of aquaporin 4, showed the localization to the subpial region and ependyma with increased immunoreactivity in the brains of CO2 exposed rats. This work was supported by awards NNX15AW48G to S.Z. Animal tissue and live data was provided under a tissue/data sharing agreement with Dr. Charles Fuller, UC Davis.

S B Zanello↗