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1.
Exp Physiol ; 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38180298

RESUMO

Space exploration involves many dangers including galactic cosmic radiation (GCR). This class of radiation includes high-energy protons and heavy ionizing ions. NASA has defined GCR as a carcinogenic risk for long-duration space missions. To date, no clear strategy has been developed to counter chronic GCR exposure. We hypothesize that preconditioning cells with low levels of radiation will be protective from subsequent higher radiation exposures. H9C2 cells were pretreated with 0.1 to 1.0 Gy X-rays. The challenge radiation exposure consisted of either 8 Gy X-rays or 75 cGy of GCR, using a five-ion GCRsim protocol. A cell doubling time assay was used to determine cell viability. An 8 Gy X-ray challenge alone significantly (P < 0.05) increased cell doubling time compared to the no-radiation control group. Low-dose radiation pre-treatment ameliorated the 8 Gy X-ray-induced increases in cell doubling time. A 75 cGy GCR challenge alone significantly increased cell doubling time compared to the no-radiation group. Following the 75 cGy challenge, only the 0.5 and 1.0 Gy pre-treatment ameliorated the 75 cGy-induced increases in cell doubling time. DNA damage or pathological oxidant stress will delay replicative functions and increase cell doubling time. Our results suggested that pretreatment with low-dose X-rays induced an adaptive response which offered a small but significant protection against a following higher radiation challenge. Although perhaps not a practical countermeasure, these findings may serve to offer insight into cell signalling pathways activated in response to low-dose irradiation and targeted for countermeasure development.

2.
Int J Mol Sci ; 25(19)2024 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-39408667

RESUMO

Human exploration of the solar system will expose crew members to galactic cosmic radiation (GCR), with a potential for adverse health effects. GCR particles (protons and ions) move at nearly the speed of light and easily penetrate space station walls, as well as the human body. Previously, we have shown reactivation of latent herpesviruses, including herpes simplex virus, Varicella zoster virus, Epstein-Barr virus, and cytomegalovirus (CMV), during stays at the International Space Station. Given the prevalence of latent CMV and the known propensity of space radiation to cause alterations in many cellular processes, we undertook this study to understand the role of GCR in reactivating latent CMV. Latently infected Kasumi cells with CMV were irradiated with 137Cs gamma rays, 150 MeV protons, 600 MeV/n carbon ions, 600 MeV/n iron ions, proton ions, and simulated GCR. The CMV copy number increased significantly in the cells exposed to radiation as compared with the non-irradiated controls. Viral genome sequencing did not reveal significant nucleotide differences among the compared groups. However, transcriptome analysis showed the upregulation of transcription of the UL49 ORF, implicating it in the switch from latent to lytic replication. These findings support our hypothesis that GCR may be a strong contributor to the reactivation of CMV infection seen in ISS crew members.


Assuntos
Radiação Cósmica , Citomegalovirus , Ativação Viral , Replicação Viral , Radiação Cósmica/efeitos adversos , Citomegalovirus/fisiologia , Citomegalovirus/efeitos da radiação , Humanos , Replicação Viral/efeitos da radiação , Ativação Viral/efeitos da radiação , Latência Viral/efeitos da radiação , Genoma Viral , Raios gama , Infecções por Citomegalovirus/virologia , Linhagem Celular
3.
Int J Mol Sci ; 25(17)2024 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-39273325

RESUMO

Cosmic radiation experienced during space travel may increase the risk of cognitive impairment. While simulated galactic cosmic radiation (GCRsim) has led to memory deficits in wildtype (WT) mice, it has not been investigated whether GCRsim in combination with genetic risk factors for Alzheimer's disease (AD) worsens memory further in aging mice. Here, we investigated the central nervous system (CNS) effects of 0 Gy (sham) or 0.75 Gy five-ion GCRsim or 2 Gy gamma radiation (IRR) in 14-month-old female and male APPNL-F/NL-F knock-in (KI) mice bearing humanized ApoE3 or ApoE4 (APP;E3F and APP;E4F). As travel to a specialized facility was required for irradiation, both traveled sham-irradiated C57BL/6J WT and KI mice and non-traveled (NT) KI mice acted as controls for potential effects of travel. Mice underwent four behavioral tests at 20 months of age and were euthanized for pathological and biochemical analyses 1 month later. Fecal samples were collected pre- and post-irradiation at four different time points. GCRsim seemed to impair memory in male APP;E3F mice compared to their sham counterparts. Travel tended to improve cognition in male APP;E3F mice and lowered total Aß in female and male APP;E3F mice compared to their non-traveled counterparts. Sham-irradiated male APP;E4F mice accumulated more fibrillar amyloid than their APP;E3F counterparts. Radiation exposure had only modest effects on behavior and brain changes, but travel-, sex-, and genotype-specific effects were seen. Irradiated mice had immediate and long-term differences in their gut bacterial composition that correlated to Alzheimer's disease phenotypes.


Assuntos
Doença de Alzheimer , Precursor de Proteína beta-Amiloide , Cognição , Radiação Cósmica , Camundongos Transgênicos , Animais , Feminino , Masculino , Radiação Cósmica/efeitos adversos , Camundongos , Cognição/efeitos da radiação , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Doença de Alzheimer/genética , Doença de Alzheimer/etiologia , Doença de Alzheimer/metabolismo , Técnicas de Introdução de Genes , Camundongos Endogâmicos C57BL , Apolipoproteínas E/genética , Apolipoproteínas E/metabolismo , Modelos Animais de Doenças , Fatores Sexuais , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/metabolismo , Humanos
4.
Radiat Environ Biophys ; 61(4): 631-637, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36167896

RESUMO

Gastrointestinal (GI) cancer risk among astronauts after encountering galactic cosmic radiation (GCR) is predicted to exceed safe permissible limits in long duration deep-space missions. Current predictions are based on relative biological effectiveness (RBE) values derived from in-vivo studies using single-ion beams, while GCR is essentially a mixed radiation field composed of protons (H), helium (He), and heavy ions. Therefore, a sequentially delivered proton (H) → Helium (He) → Oxygen (O) → Silicon (Si) beam was designed to simulate simplified-mixed-field GCR (Smf-GCR), and Apc1638N/+ mice were total-body irradiated to sham or γ (157Cs) or Smf-GCR followed by assessment of GI-tumorigenesis at 150 days post-exposure. Further, GI-tumor data from equivalent doses of heavy-ions (i.e., 0.05 Gy of O and Si) in 0.5 Gy of Smf-GCR were compared to understand the contributions of heavy-ions in GI-tumorigenesis. The Smf-GCR-induced tumor and carcinoma count were significantly greater than γ-rays, and male preponderance for GI-tumorigenesis was consistent with our earlier findings. Comparison of tumor data from Smf-GCR and equivalent doses of heavy ions revealed an association between higher GI-tumorigenesis where dose received from heavy-ions contributed to > 95% of the total GI-tumorigenic effect observed after Smf-GCR. This study provides the first experimental evidence that cancer risk after GCR exposure could largely depend on doses received from constituent heavy-ions.


Assuntos
Radiação Cósmica , Íons Pesados , Neoplasias Induzidas por Radiação , Exposição à Radiação , Voo Espacial , Camundongos , Masculino , Animais , Íons Pesados/efeitos adversos , Hélio , Radiação Cósmica/efeitos adversos , Neoplasias Induzidas por Radiação/etiologia , Neoplasias Induzidas por Radiação/patologia , Carcinogênese , Prótons
5.
J Radiol Prot ; 42(2)2022 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-35263735

RESUMO

The International Commission on Radiation Units and Measurements recently proposed new operational quantities for external radiation exposure. Among those, the ambient dose is intended to replace the ambient dose equivalent as estimator for the effective dose. Following its definition, the measurement of the ambient dose requires a much more detailed knowledge about the radiation field than the ambient dose equivalent. The implications for radiation protection in aviation concerning galactic cosmic radiation that would follow the adoption of the ambient dose as operational quantity at flight altitudes were investigated in this work using model calculations. It was found that the ambient dose is about 10% higher than the ambient dose equivalent for conditions relevant in commercial aviation and overestimates the effective dose by about 30%.


Assuntos
Aviação , Radiação Cósmica , Exposição Ocupacional , Monitoramento de Radiação , Aeronaves , Altitude , Exposição Ocupacional/análise , Doses de Radiação
6.
Neurobiol Learn Mem ; 178: 107367, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33359392

RESUMO

Deep space travel presents a number of measurable risks including exposure to a spectrum of radiations of varying qualities, termed galactic cosmic radiation (GCR) that are capable of penetrating the spacecraft, traversing through the body and impacting brain function. Using rodents, studies have reported that exposure to simulated GCR leads to cognitive impairments associated with changes in hippocampus function that can persist as long as one-year post exposure with no sign of recovery. Whether memory can be updated to incorporate new information in mice exposed to GCR is unknown. Further, mechanisms underlying long lasting impairments in cognitive function as a result of GCR exposure have yet to be defined. Here, we examined whether whole body exposure to simulated GCR using 6 ions and doses of 5 or 30 cGy interfered with the ability to update an existing memory or impact hippocampal synaptic plasticity, a cellular mechanism believed to underlie memory processes, by examining long term potentiation (LTP) in acute hippocampal slices from middle aged male mice 3.5-5 months after radiation exposure. Using a modified version of the hippocampus-dependent object location memory task developed by our lab termed "Objects in Updated Locations" (OUL) task we find that GCR exposure impaired hippocampus-dependent memory updating and hippocampal LTP 3.5-5 months after exposure. Further, we find that impairments in LTP are reversed through one-time systemic subcutaneous injection of the histone deacetylase 3 inhibitor RGFP 966 (10 mg/kg), suggesting that long lasting impairments in cognitive function may be mediated at least in part, through epigenetic mechanisms.


Assuntos
Hipocampo/efeitos dos fármacos , Inibidores de Histona Desacetilases/farmacologia , Memória/efeitos dos fármacos , Plasticidade Neuronal/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Acrilamidas/farmacologia , Animais , Radiação Cósmica , Hipocampo/efeitos da radiação , Histona Desacetilases , Masculino , Memória/efeitos da radiação , Camundongos , Plasticidade Neuronal/efeitos da radiação , Neurônios/efeitos da radiação , Fenilenodiaminas/farmacologia , Exposição à Radiação
7.
Molecules ; 25(18)2020 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-32971937

RESUMO

Innovative multifunctional materials that combine structural functionality with other spacecraft subsystem functions have been identified as a key enabling technology for future deep space missions. In this work, we report the structure and performance of multifunctional polymer matrix composites developed for aerospace applications that require both structural functionality and space radiation shielding. Composites comprised of ultra-high molecular weight polyethylene (UHMWPE) fiber reinforcement and a hydrogen-rich polybenzoxazine matrix are prepared using a low-pressure vacuum bagging process. The polybenzoxazine matrix is derived from a novel benzoxazine resin that possesses a unique combination of attributes: high hydrogen concentration for shielding against galactic cosmic rays (GCR), low polymerization temperature to prevent damage to UHMWPE fibers during composite fabrication, long shelf-life, and low viscosity to improve flow during molding. Dynamic mechanical analysis (DMA) is used to study rheological and thermomechanical properties. Composite mechanical properties, obtained using several standardized tests, are reported. Improvement in composite stiffness, through the addition of carbon fiber skin layers, is investigated. Radiation shielding performance is evaluated using computer-based simulations. The composites demonstrate clear advantages over benchmark materials in terms of combined structural and radiation shielding performance.


Assuntos
Benzoxazinas/química , Benzoxazinas/farmacologia , Meio Ambiente Extraterreno , Protetores contra Radiação/química , Protetores contra Radiação/farmacologia , Radiação Cósmica/efeitos adversos , Testes Mecânicos , Polietilenos/química , Polimerização , Temperatura de Transição
8.
Int J Mol Sci ; 19(10)2018 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-30304778

RESUMO

High-charge and -energy (HZE) particles comprise space radiation and they pose a challenge to astronauts on deep space missions. While exposure to most HZE particles decreases neurogenesis in the hippocampus-a brain structure important in memory-prior work suggests that 12C does not. However, much about 12C's influence on neurogenesis remains unknown, including the time course of its impact on neurogenesis. To address this knowledge gap, male mice (9⁻11 weeks of age) were exposed to whole-body 12C irradiation 100 cGy (IRR; 1000 MeV/n; 8 kEV/µm) or Sham treatment. To birthdate dividing cells, mice received BrdU i.p. 22 h post-irradiation and brains were harvested 2 h (Short-Term) or three months (Long-Term) later for stereological analysis indices of dentate gyrus neurogenesis. For the Short-Term time point, IRR mice had fewer Ki67, BrdU, and doublecortin (DCX) immunoreactive (+) cells versus Sham mice, indicating decreased proliferation (Ki67, BrdU) and immature neurons (DCX). For the Long-Term time point, IRR and Sham mice had similar Ki67+ and DCX+ cell numbers, suggesting restoration of proliferation and immature neurons 3 months post-12C irradiation. IRR mice had fewer surviving BrdU+ cells versus Sham mice, suggesting decreased cell survival, but there was no difference in BrdU+ cell survival rate when compared within treatment and across time point. These data underscore the ability of neurogenesis in the mouse brain to recover from the detrimental effect of 12C exposure.


Assuntos
Giro Denteado/citologia , Giro Denteado/efeitos da radiação , Células Piramidais/metabolismo , Células Piramidais/efeitos da radiação , Irradiação Corporal Total , Animais , Biomarcadores , Isótopos de Carbono , Contagem de Células , Proliferação de Células , Sobrevivência Celular , Proteína Duplacortina , Imuno-Histoquímica , Antígeno Ki-67/metabolismo , Camundongos , Neurogênese , Células Piramidais/citologia
9.
Int J Mol Sci ; 19(4)2018 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-29677125

RESUMO

The space radiation environment includes helium (4He) ions that may impact brain function. As little is known about the effects of exposures to 4He ions on the brain, we assessed the behavioral and cognitive performance of C57BL/6J × DBA2/J F1 (B6D2F1) mice three months following irradiation with 4He ions (250 MeV/n; linear energy transfer (LET) = 1.6 keV/μm; 0, 21, 42 or 168 cGy). Sham-irradiated mice and mice irradiated with 21 or 168 cGy showed novel object recognition, but mice irradiated with 42 cGy did not. In the passive avoidance test, mice received a slight foot shock in a dark compartment, and latency to re-enter that compartment was assessed 24 h later. Sham-irradiated mice and mice irradiated with 21 or 42 cGy showed a higher latency on Day 2 than Day 1, but the latency to enter the dark compartment in mice irradiated with 168 cGy was comparable on both days. 4He ion irradiation, at 42 and 168 cGy, reduced the levels of the dendritic marker microtubule-associated protein-2 (MAP-2) in the cortex. There was an effect of radiation on apolipoprotein E (apoE) levels in the hippocampus and cortex, with higher apoE levels in mice irradiated at 42 cGy than 168 cGy and a trend towards higher apoE levels in mice irradiated at 21 than 168 cGy. In addition, in the hippocampus, there was a trend towards a negative correlation between MAP-2 and apoE levels. While reduced levels of MAP-2 in the cortex might have contributed to the altered performance in the passive avoidance test, it does not seem sufficient to do so. The higher hippocampal and cortical apoE levels in mice irradiated at 42 than 168 cGy might have served as a compensatory protective response preserving their passive avoidance memory. Thus, there were no alterations in behavioral performance in the open filed or depressive-like behavior in the forced swim test, while cognitive impairments were seen in the object recognition and passive avoidance tests, but not in the contextual or cued fear conditioning tests. Taken together, the results indicate that some aspects of cognitive performance are altered in male mice exposed to 4He ions, but that the response is task-dependent. Furthermore, the sensitive doses can vary within each task in a non-linear fashion. This highlights the importance of assessing the cognitive and behavioral effects of charged particle exposure with a variety of assays and at multiple doses, given the possibility that lower doses may be more damaging due to the absence of induced compensatory mechanisms at higher doses.


Assuntos
Cognição/efeitos da radiação , Disfunção Cognitiva/etiologia , Hélio/efeitos adversos , Proteínas Associadas aos Microtúbulos/metabolismo , Animais , Apolipoproteínas E/metabolismo , Disfunção Cognitiva/fisiopatologia , Relação Dose-Resposta à Radiação , Hélio/uso terapêutico , Hipocampo/metabolismo , Hipocampo/efeitos da radiação , Masculino , Memória/efeitos da radiação , Camundongos , Camundongos Endogâmicos C57BL
10.
Z Med Phys ; 34(1): 111-139, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37225603

RESUMO

Ionizing radiation in general and mixed fields of space radiation in particular pose a risk of serious harm to human health. The risk of such adverse effects increases with the duration of the mission, and for all missions outside the protective properties of the Earth's magnetic field and atmosphere. Accordingly, radiation protection is of central importance for all human spaceflight, which is recognized by all international space agencies. To date various systems, analyze and determine the exposure to ionizing radiation within the environment and to the crew onboard the International Space Station (ISS). In addition to this operational monitoring, experiments and technology demonstrations are carried out. This to further enhance systems capabilities, to prepare for exploratory missions, to the Deep Space Gateway and/or to enable for human presence at other celestial bodies. Subsequently the European Space Agency (ESA) decided early to support the development of an active personal dosimeter. Under the auspices of the European Space Research and Technology Center (ESTEC) together with the European Astronaut Center's (EAC) Medical Operations and Space Medicine (HRE-OM) team, a European industrial consortium was formed to develop, build, and test this system. To complete the ESA Active Dosimeter (EAD) Technology Demonstration in space, EAD components were delivered to ISS with the ESA's space missions 'iriss' and 'proxima' in 2015 and 2016. This marked Phase 1 (2015) and 2 (2016-2017) of the EAD Technology Demonstration to which focus is given in this publication. All EAD systems and their functionalities, the different radiation detector, their properties, and calibrations procedures are described. Emphasis is first on the "iriss" mission of September 2015, that provided a complete set of data for an entire space mission from launch to landing, for the first time. Data obtained during Phase 2 in 2016-2017 are discussed thereafter. Measurements with the active radiation detectors of the EAD system provided data of the absorbed dose, dose equivalent, quality factor as well as the various dose contributions during the crossings of the South Atlantic Anomaly (SAA) and/or resulting from galactic cosmic radiation (GCR). Results of the in-flight cross-calibrations among the internal sensors of the EAD systems are discussed and alternative usage of the EAD Mobile Units as area monitors at various different locations inside the ISS is described.


Assuntos
Radiação Cósmica , Monitoramento de Radiação , Voo Espacial , Humanos , Dosímetros de Radiação , Monitoramento de Radiação/métodos , Astronautas , Doses de Radiação
11.
Life Sci Space Res (Amst) ; 36: 116-122, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36682820

RESUMO

Female astronauts inevitably exposed to galactic cosmic radiation (GCR) are considered at a greater risk for mammary cancer development. The purpose of this study is to assess the status of mammary cancer-associated preneoplasia markers after GCR and γ-ray irradiation using a mouse model of human mammary cancer. Female ApcMin/+ mice were irradiated to 50 cGy of either γ-ray (137Cs) or full-spectrum simulated galactic cosmic radiation (GCR) (33-beam), and at 110 - 120 days post-irradiation mice were euthanized, and normal-appearing mammary tissues were analyzed for histological and molecular markers of preneoplasia. Whole-mount staining, hematoxylin and eosin-based histological assessment, and Cyclin D1 immunohistochemistry (IHC) were performed to analyze ductal outgrowth and cell proliferation. Additionally, mRNA expression of known mammary preneoplasia markers (Muc1, Exo1, Foxm1, Depdc1a, Nusap1, Spp1, and Rrm2) was analyzed using qPCR, and their respective protein expression was validated using immunohistochemistry. A significant increase in ductal outgrowth and cell proliferation in mammary tissues of GCR-irradiated mice was noted which indicates a higher risk of mammary cancer, relative to γ-rays. Increased mRNA and protein expression of Spp1 was observed in the GCR group, relative to γ-rays. This study demonstrates the plausibility of Spp1 as a preneoplasia marker in the early detection of mammary cancer after space radiation exposure.


Assuntos
Neoplasias da Mama , Radiação Cósmica , Voo Espacial , Feminino , Humanos , Astronautas , Mama , Radiação Cósmica/efeitos adversos , Osteopontina , Animais , Camundongos
12.
Life Sci Space Res (Amst) ; 39: 14-25, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37945085

RESUMO

Two DOSimetry TELescopes (DOSTELs) have been measuring the radiation environment in the Columbus module of the International Space Station (ISS) since 2009 in the frame of the DOSIS and DOSIS 3D projects. Both instruments have measured the charged particle flux rate and dose rates in a telescope geometry of two planar silicon detectors. The radiation environment in the ISS orbit is mostly composed by galactic cosmic radiation (GCR) and its secondary radiation and protons from the inner radiation belt in the South Atlantic Anomaly (SAA) with sporadic contributions of solar energetic particles at high latitudes. The data presented in this work cover two solar activity minima and corresponding GCR intensity maxima in 2009 and 2020 and the solar activity maximum and corresponding GCR intensity minimum in 2014/2015. Average dose rates measured in the Columbus laboratory in the ISS orbit from GCR and SAA are presented separately. The data is analyzed with respect to the effective magnetic shielding and grouped into different cut-off rigidity intervals. Using only measurements in magnetically unshielded regions at low cut-off rigidity and applying a factor for the geometrical shielding of the Earth, absorbed dose rates and dose equivalent rates in near-Earth interplanetary space are estimated for the years 2009 to 2022.


Assuntos
Radiação Cósmica , Monitoramento de Radiação , Voo Espacial , Astronave , Doses de Radiação , Monitoramento de Radiação/métodos , Radiometria , Atividade Solar
13.
Life (Basel) ; 13(3)2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36983945

RESUMO

Space missions with humans expose the crews to ionizing radiation, mainly due to the galactic cosmic radiation (GCR). All radiation protection programs in space aim to minimize crews' exposure to radiation. The radiation protection of astronauts can be achieved through the use of shields. The shields could serve as a suit to reduce GCR exposure and, in an emergency, as a radiation shelter to perform necessary interventions outside the space habitat in case of a solar proton event (SPE). A space radiation shielding that is suitable for exploration during space missions requires particular features and a proper knowledge of the radiation type. This study shows the results of numerical simulations performed with the Geant4 toolkit-based code DOSE. Calculations to evaluate the performance of Nomex, an aramidic fiber with high mechanical resistance, in terms of dose reduction to crews, were performed considering the interaction between protons with an energy spectrum ranging from 50 to 1100 MeV and a target slab of 20 g/cm2. This paper shows the properties of secondary products obtained as a result of the interaction between space radiation and a Nomex target and the properties of the secondary particles that come out the shield. The results of this study show that Nomex can be considered a good shield candidate material in terms of dose reductions. We also note that the secondary particles that provide the greatest contribution to the dose are protons, neutrons and, in a very small percentage, α-particles and Li ions.

14.
Life (Basel) ; 13(3)2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36983950

RESUMO

Missions into deep space will expose astronauts to the harsh space environment, and the degenerative tissue effects of space radiation are largely unknown. To assess the risks, in this study, male BALB/c mice were exposed to 500 mGy 5-ion simulated GCR (GCRsim) at the NASA Space Radiation Laboratory. In addition, male and female CD1 mice were exposed to GCRsim and administered a diet containing Transforming Growth Factor-beta (TGF-ß)RI kinase (ALK5) inhibitor IPW-5371 as a potential countermeasure. An ultrasound was performed to investigate cardiac function. Cardiac tissue was collected to determine collagen deposition, the density of the capillary network, and the expression of the immune mediator toll-like receptor 4 (TLR4) and immune cell markers CD2, CD4, and CD45. In male BALB/c mice, the only significant effects of GCRsim were an increase in the CD2 and TLR4 markers. In male CD1 mice, GCRsim caused a significant increase in total collagens and a decrease in the expression of TLR4, both of which were mitigated by the TGF-ß inhibitor diet. In female CD1 mice, GCRsim caused an increase in the number of capillaries per tissue area in the ventricles, which may be explained by the decrease in the left ventricular mass. However, this increase was not mitigated by TGF-ß inhibition. In both male and female CD1 mice, the combination of GCRsim and TGF-ß inhibition caused changes in left ventricular immune cell markers that were not seen with GCRsim alone. These data suggest that GCRsim results in minor changes to cardiac tissue in both an inbred and outbred mouse strain. While there were few GCRsim effects to be mitigated, results from the combination of GCRsim and the TGF-ß inhibitor do point to a role for TGF-ß in maintaining markers of immune cells in the heart after exposure to GCR.

15.
Front Neurosci ; 16: 908632, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36561122

RESUMO

Space exploration has advanced substantially over recent decades and plans to increase the duration of deep space missions are in preparation. One of the primary health concerns is potential damage to the central nervous system (CNS), resulting in loss of cognitive abilities and function. The majority of ground-based research on space radiation-induced health risks has been conducted using single particle simulations, which do not effectively model real-world scenarios. Thus, to improve the safety of space missions, we must expand our understanding of the effects of simulated galactic cosmic rays (GCRs) on the CNS. To assess the effects of low-dose GCR, we subjected 6-month-old male BALB/c mice to 50 cGy 5-beam simplified GCR spectrum (1H, 28Si, 4He, 16O, and 56Fe) whole-body irradiation at the NASA Space Radiation Laboratory. Animals were tested for cognitive performance with Y-maze and Morris water maze tests 3 months after irradiation. Irradiated animals had impaired short-term memory and lacked spatial memory retention on day 5 of the probe trial. Glial cell analysis by flow cytometry showed no significant changes in oligodendrocytes, astrocytes, microglia or neural precursor cells (NPC's) between the sham group and GCR group. Bone marrow cytogenetic data showed a significant increase in the frequency of chromosomal aberrations after GCR exposure. Finally, tandem mass tag proteomics identified 3,639 proteins, 113 of which were differentially expressed when comparing sham versus GCR exposure (fold change > 1.5; p < 0.05). Our data suggest exposure to low-dose GCR induces cognitive deficits by impairing short-term memory and spatial memory retention.

16.
Life Sci Space Res (Amst) ; 35: 76-87, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36336373

RESUMO

Space travel increases galactic cosmic ray exposure to flight crews and this is significantly elevated once travel moves beyond low Earth orbit. This includes combinations of high energy protons and heavy ions such as 56Fe or 16O. There are distinct differences in the biological response to low-energy transfer (x-rays) or high-energy transfer (High-LET). However, given the relatively low fluence rate of exposure during flight operations, it might be possible to manage these deleterious effects using small molecules currently available. Virtually all reports to date examining small molecule management of radiation exposure are based on low-LET challenges. To that end an FDA approved drug library (725 drugs) was used to perform a high throughput screen of cultured cells following exposure to galactic cosmic radiation. The H9c2 myoblasts, ES-D3 pluripotent cells, and Hy926 endothelial cell lines were exposed to a single exposure (75 cGy) using the 5-ion GCRsim protocol developed at the NASA Space Radiation Laboratory (NSRL). Following GCR exposure cells were maintained for up to two weeks. For each drug (@10µM), a hierarchical cumulative score was developed incorporating measures of mitochondrial and cellular function, oxidant stress and cell senescence. The top 160 scores were retested following a similar protocol using 1µM of each drug. Within the 160 drugs, 33 are considered to have an anti-inflammatory capacity, while others also indirectly suppressed pro-inflammatory pathways or had noted antioxidant capacity. Lead candidates came from different drug classes that included angiotensin converting enzyme inhibitors or AT1 antagonists, COX2 inhibitors, as well as drugs mediated by histamine receptors. Surprisingly, different classes of anti-diabetic medications were observed to be useful including sulfonylureas and metformin. Using a hierarchical decision structure, we have identified several lead candidates. That no one drug or even drug class was completely successful across all parameters tested suggests the complexity of managing the consequences of galactic cosmic radiation exposure.


Assuntos
Radiação Cósmica , Íons Pesados , Voo Espacial , Radiação Cósmica/efeitos adversos , Transferência Linear de Energia , Prótons
17.
Life Sci Space Res (Amst) ; 33: 58-68, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35491030

RESUMO

The exposure to galactic cosmic radiation (GCR) is a major health concern for astronauts. Crewed missions with durations of several years are foreseen in future space exploration projects such as permanent habitats on the Moon and flights to Mars. This aim requires elaborate space radiation shielding concepts and a proper understanding of the underlying radiation physics and radiobiology as well as their interplay. In the present work, Monte Carlo simulations to assess the performance of different materials (polyethylene, aluminum, Moon regolith) as thick shields (up to 400 g/cm2) against GCR were conducted using the FLUKA code. Absorbed dose, dose equivalent and the mean quality factor at 1 cm depth in the ICRU sphere as a function of shielding thickness were calculated in a spherical shell configuration for both solar minimum and solar maximum GCR conditions. Large differences were observed in the performance of the studied materials as thick GCR shields. Special attention was paid to the build-up and moderation of secondary neutrons. A method to reduce the neutron contributions to ambient dose equivalent by means of a two-layer shielding combination is proposed. The present study can be useful for considerations on thick shielding of Moon or Mars habitats built from local regolith.


Assuntos
Radiação Cósmica , Voo Espacial , Astronautas , Radiação Cósmica/efeitos adversos , Humanos , Método de Monte Carlo , Nêutrons
18.
Front Public Health ; 9: 733337, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34820349

RESUMO

Space radiobiology is an interdisciplinary science that examines the biological effects of ionizing radiation on humans involved in aerospace missions. The dose-effect models are one of the relevant topics of space radiobiology. Their knowledge is crucial for optimizing radioprotection strategies (e.g., spaceship and lunar space station-shielding and lunar/Mars village design), the risk assessment of the health hazard related to human space exploration, and reducing damages induced to astronauts from galactic cosmic radiation. Dose-effect relationships describe the observed damages to normal tissues or cancer induction during and after space flights. They are developed for the various dose ranges and radiation qualities characterizing the actual and the forecast space missions [International Space Station (ISS) and solar system exploration]. Based on a Pubmed search including 53 papers reporting the collected dose-effect relationships after space missions or in ground simulations, 7 significant dose-effect relationships (e.g., eye flashes, cataract, central nervous systems, cardiovascular disease, cancer, chromosomal aberrations, and biomarkers) have been identified. For each considered effect, the absorbed dose thresholds and the uncertainties/limitations of the developed relationships are summarized and discussed. The current knowledge on this topic can benefit from further in vitro and in vivo radiobiological studies, an accurate characterization of the quality of space radiation, and the numerous experimental dose-effects data derived from the experience in the clinical use of ionizing radiation for diagnostic or treatments with doses similar to those foreseen for the future space missions. The growing number of pooled studies could improve the prediction ability of dose-effect relationships for space exposure and reduce their uncertainty level. Novel research in the field is of paramount importance to reduce damages to astronauts from cosmic radiation before Beyond Low Earth Orbit exploration in the next future. The study aims at providing an overview of the published dose-effect relationships and illustrates novel perspectives to inspire future research.


Assuntos
Radiação Cósmica , Astronautas , Radiação Cósmica/efeitos adversos , Humanos , Doses de Radiação , Radiobiologia
19.
Front Microbiol ; 12: 748950, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34690999

RESUMO

To enhance the gastrointestinal health of astronauts, probiotic microorganisms are being considered for inclusion on long-duration human missions to the Moon and Mars. Here we tested three commercial probiotics-Bifidobacterium longum strain BB536, Lactobacillus acidophilus strain DDS-1, and spores of Bacillus subtilis strain HU58-for their survival to some of the conditions expected to be encountered during a 3-year, round trip voyage to Mars. All probiotics were supplied as freeze-dried cells in capsules at a titer of >109 colony forming units per capsule. Parameters tested were survival to: (i) long-term storage at ambient conditions, (ii) simulated Galactic Cosmic Radiation and Solar Particle Event radiation provided by the NASA Space Radiation Laboratory, (iii) exposure to simulated gastric fluid, and (iv) exposure to simulated intestinal fluid. We found that radiation exposure produced minimal effects on the probiotic strains. However, we found that that the shelf-lives of the three strains, and their survival during passage through simulations of the upper GI tract, differed dramatically. We observed that only spores of B. subtilis were capable of surviving all conditions and maintaining a titer of >109 spores per capsule. The results indicate that probiotics consisting of bacterial spores could be a viable option for long-duration human space travel.

20.
Behav Brain Res ; 400: 113010, 2021 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-33181183

RESUMO

Deep space flight missions beyond the Van Allen belt have the potential to expose astronauts to space radiation which may damage the central nervous system and impair function. The proposed mission to Mars will be the longest mission-to-date and identifying mission critical tasks that are sensitive to space radiation is important for developing and evaluating the efficacy of counter measures. Fine motor control has been assessed in humans, rats, and many other species using string-pulling behavior. For example, focal cortical damage has been previously shown to disrupt the topographic (i.e., path circuity) and kinematic (i.e., moment-to-moment speed) organization of rat string-pulling behavior count to compromise task accuracy. In the current study, rats were exposed to a ground-based model of simulated space radiation (5 cGy 28Silicon), and string-pulling behavior was used to assess fine motor control. Irradiated rats initially took longer to pull an unweighted string into a cage, exhibited impaired accuracy in grasping the string, and displayed postural deficits. Once rats were switched to a weighted string, some deficits lessened but postural instability remained. These results demonstrate that a single exposure to a low dose of space radiation disrupts skilled hand movements and posture, suggestive of neural impairment. This work establishes a foundation for future studies to investigate the neural structures and circuits involved in fine motor control and to examine the effectiveness of counter measures to attenuate the effects of space radiation on fine motor control.


Assuntos
Comportamento Animal/fisiologia , Radiação Cósmica/efeitos adversos , Meio Ambiente Extraterreno , Destreza Motora/fisiologia , Equilíbrio Postural/fisiologia , Lesões Experimentais por Radiação/fisiopatologia , Animais , Fenômenos Biomecânicos , Humanos , Masculino , Ratos , Ratos Wistar
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