Translation from Microgravity Research to Earth Application

Topic Information

Dear Colleagues,

Microgravity provides a unique research environment and an opportunity to identify cellular mechanisms involved in gravity-sensing, regulation and adaptation responses at the cellular, tissue and organism level, covering animals, plants and humans. Microgravity research is, in many cases, a continuation of ground-based studies in microgravity analogues and simulations, as well as under increased gravitational (hypergravity) conditions, providing comprehensive and new knowledge on the regulation of cellular and sub-cellular functioning.  Furthermore, the microgravity environment is characterized by a lack of sedimentation, which facilitates the assembly of 3D cell constructions and bioprinting with innovative potential applications in tissue and bioengineering techniques. A prerequisite for long-lasting deep space missions is the knowledge of the effect of microgravity on key biological systems, such as the immune, musculoskeletal, cardiovascular, neurosensory, neuroendocrine, excretory, respiratory system, their metabolism and homeostasis, focusing on molecular/cellular processes, but also the development of life support systems. There are many indications and already findings that pathophysiological changes observed during and after spaceflight represent models of a series of chronic diseases known from Earth. This Topic provides examples from microgravity studies with potential applications to Earth-related issues.

Dr. Daniela Grimm
Dr. Ruth Hemmersbach
Topic Editors

Participating Journals

Journal Name	Impact Factor	CiteScore	Launched Year	First Decision (median)	APC
Biomedicines biomedicines	4.7	3.7	2013	15.4 Days	CHF 2600
International Journal of Molecular Sciences ijms	5.6	7.8	2000	16.3 Days	CHF 2900

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6 pages, 225 KiB  

Open AccessEditorial

Translation from Microgravity Research to Earth Application

by Daniela Grimm and Ruth Hemmersbach

Int. J. Mol. Sci. 2022, 23(19), 10995; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms231910995 - 20 Sep 2022

Cited by 4 | Viewed by 1307

Abstract

The topic “Translation from Microgravity Research to Earth Application” comprises publications focusing on space life sciences, gravitational biology and space medicine [...] Full article

(This article belongs to the Topic Translation from Microgravity Research to Earth Application)

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15 pages, 780 KiB  

Open AccessArticle

Validating Causal Diagrams of Human Health Risks for Spaceflight: An Example Using Bone Data from Rodents

by Robert J. Reynolds, Ryan T. Scott, Russell T. Turner, Urszula T. Iwaniec, Mary L. Bouxsein, Lauren M. Sanders and Erik L. Antonsen

Biomedicines 2022, 10(9), 2187; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10092187 - 05 Sep 2022

Cited by 6 | Viewed by 2888

Abstract

As part of the risk management plan for human system risks at the US National Aeronautics and Space Administration (NASA), the NASA Human Systems Risk Board uses causal diagrams (in the form of directed, acyclic graphs, or DAGs) to communicate the complex web [...] Read more.

As part of the risk management plan for human system risks at the US National Aeronautics and Space Administration (NASA), the NASA Human Systems Risk Board uses causal diagrams (in the form of directed, acyclic graphs, or DAGs) to communicate the complex web of events that leads from exposure to the spaceflight environment to performance and health outcomes. However, the use of DAGs in this way is relatively new at NASA, and thus far, no method has been articulated for testing their veracity using empirical data. In this paper, we demonstrate a set of procedures for doing so, using (a) a DAG related to the risk of bone fracture after exposure to spaceflight; and (b) four datasets originally generated to investigate this phenomenon in rodents. Tests of expected marginal correlation and conditional independencies derived from the DAG indicate that the rodent data largely agree with the structure of the diagram. Incongruencies between tests and the expected relationships in one of the datasets are likely explained by inadequate representation of a key DAG variable in the dataset. Future directions include greater tie-in with human data sources, including multiomics data, which may allow for more robust characterization and measurement of DAG variables. Full article

(This article belongs to the Topic Translation from Microgravity Research to Earth Application)

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30 pages, 6083 KiB  

Open AccessArticle

Hypergravity Attenuates Reactivity in Primary Murine Astrocytes

by Yannick Lichterfeld, Laura Kalinski, Sarah Schunk, Theresa Schmakeit, Sebastian Feles, Timo Frett, Harald Herrmann, Ruth Hemmersbach and Christian Liemersdorf

Biomedicines 2022, 10(8), 1966; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10081966 - 13 Aug 2022

Cited by 10 | Viewed by 2317

Abstract

Neuronal activity is the key modulator of nearly every aspect of behavior, affecting cognition, learning, and memory as well as motion. Hence, disturbances of the transmission of synaptic signals are the main cause of many neurological disorders. Lesions to nervous tissues are associated [...] Read more.

Neuronal activity is the key modulator of nearly every aspect of behavior, affecting cognition, learning, and memory as well as motion. Hence, disturbances of the transmission of synaptic signals are the main cause of many neurological disorders. Lesions to nervous tissues are associated with phenotypic changes mediated by astrocytes becoming reactive. Reactive astrocytes form the basis of astrogliosis and glial scar formation. Astrocyte reactivity is often targeted to inhibit axon dystrophy and thus promote neuronal regeneration. Here, we aim to understand the impact of gravitational loading induced by hypergravity to potentially modify key features of astrocyte reactivity. We exposed primary murine astrocytes as a model system closely resembling the in vivo reactivity phenotype on custom-built centrifuges for cultivation as well as for live-cell imaging under hypergravity conditions in a physiological range (2g and 10g). We revealed spreading rates, migration velocities, and stellation to be diminished under 2g hypergravity. In contrast, proliferation and apoptosis rates were not affected. In particular, hypergravity attenuated reactivity induction. We observed cytoskeletal remodeling of actin filaments and microtubules under hypergravity. Hence, the reorganization of these key elements of cell structure demonstrates that fundamental mechanisms on shape and mobility of astrocytes are affected due to altered gravity conditions. In future experiments, potential target molecules for pharmacological interventions that attenuate astrocytic reactivity will be investigated. The ultimate goal is to enhance neuronal regeneration for novel therapeutic approaches. Full article

(This article belongs to the Topic Translation from Microgravity Research to Earth Application)

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25 pages, 6572 KiB  

Open AccessReview

Microgravity-Related Changes in Bone Density and Treatment Options: A Systematic Review

by Ronni Baran, Markus Wehland, Herbert Schulz, Martina Heer, Manfred Infanger and Daniela Grimm

Int. J. Mol. Sci. 2022, 23(15), 8650; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23158650 - 03 Aug 2022

Cited by 11 | Viewed by 3897

Abstract

Space travelers are exposed to microgravity (µg), which induces enhanced bone loss compared to the age-related bone loss on Earth. Microgravity promotes an increased bone turnover, and this obstructs space exploration. This bone loss can be slowed down by exercise on [...] Read more.

Space travelers are exposed to microgravity (µg), which induces enhanced bone loss compared to the age-related bone loss on Earth. Microgravity promotes an increased bone turnover, and this obstructs space exploration. This bone loss can be slowed down by exercise on treadmills or resistive apparatus. The objective of this systematic review is to provide a current overview of the state of the art of the field of bone loss in space and possible treatment options thereof. A total of 482 unique studies were searched through PubMed and Scopus, and 37 studies met the eligibility criteria. The studies showed that, despite increased bone formation during µg, the increase in bone resorption was greater. Different types of exercise and pharmacological treatments with bisphosphonates, RANKL antibody (receptor activator of nuclear factor κβ ligand antibody), proteasome inhibitor, pan-caspase inhibitor, and interleukin-6 monoclonal antibody decrease bone resorption and promote bone formation. Additionally, recombinant irisin, cell-free fat extract, cyclic mechanical stretch-treated bone mesenchymal stem cell-derived exosomes, and strontium-containing hydroxyapatite nanoparticles also show some positive effects on bone loss. Full article

(This article belongs to the Topic Translation from Microgravity Research to Earth Application)

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15 pages, 1220 KiB  

Open AccessReview

Joint Cartilage in Long-Duration Spaceflight

by Bergita Ganse, Magali Cucchiarini and Henning Madry

Biomedicines 2022, 10(6), 1356; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10061356 - 08 Jun 2022

Cited by 3 | Viewed by 3242

Abstract

This review summarizes the current literature available on joint cartilage alterations in long-duration spaceflight. Evidence from spaceflight participants is currently limited to serum biomarker data in only a few astronauts. Findings from analogue model research, such as bed rest studies, as well as [...] Read more.

This review summarizes the current literature available on joint cartilage alterations in long-duration spaceflight. Evidence from spaceflight participants is currently limited to serum biomarker data in only a few astronauts. Findings from analogue model research, such as bed rest studies, as well as data from animal and cell research in real microgravity indicate that unloading and radiation exposure are associated with joint degeneration in terms of cartilage thinning and changes in cartilage composition. It is currently unknown how much the individual cartilage regions in the different joints of the human body will be affected on long-term missions beyond the Low Earth Orbit. Given the fact that, apart from total joint replacement or joint resurfacing, currently no treatment exists for late-stage osteoarthritis, countermeasures might be needed to avoid cartilage damage during long-duration missions. To plan countermeasures, it is important to know if and how joint cartilage and the adjacent structures, such as the subchondral bone, are affected by long-term unloading, reloading, and radiation. The use of countermeasures that put either load and shear, or other stimuli on the joints, shields them from radiation or helps by supporting cartilage physiology, or by removing oxidative stress possibly help to avoid OA in later life following long-duration space missions. There is a high demand for research on the efficacy of such countermeasures to judge their suitability for their implementation in long-duration missions. Full article

(This article belongs to the Topic Translation from Microgravity Research to Earth Application)

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25 pages, 2432 KiB  

Open AccessReview

In Vitro Models of Bone Marrow Remodelling and Immune Dysfunction in Space: Present State and Future Directions

by Ryan Sarkar and Francesco Pampaloni

Biomedicines 2022, 10(4), 766; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10040766 - 24 Mar 2022

Cited by 8 | Viewed by 3728

Abstract

Spaceflight affects the body on every level. Reports on astronaut health identify bone marrow remodelling and dysfunction of the innate immune system as significant health risks of long-term habitation in space. Microgravity-induced alterations of the bone marrow induce physical changes to the bone [...] Read more.

Spaceflight affects the body on every level. Reports on astronaut health identify bone marrow remodelling and dysfunction of the innate immune system as significant health risks of long-term habitation in space. Microgravity-induced alterations of the bone marrow induce physical changes to the bone marrow stem cell niche. Downstream effects on innate immunity are expected due to impaired hematopoiesis and myelopoiesis. To date, few studies have investigated these effects in real microgravity and the sparsely available literature often reports contrasting results. This emphasizes a need for the development of physiologically relevant in vitro models of the bone marrow stem cell niche, capable of delivering appropriate sample sizes for robust statistics. Here, we review recent findings on the impact of spaceflight conditions on innate immunity in in vitro and animal models and discusses the latest in vitro models of the bone marrow stem cell niche and their potential translatability to gravitational biology research. Full article

(This article belongs to the Topic Translation from Microgravity Research to Earth Application)

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15 pages, 7008 KiB  

Open AccessArticle

One Year in the Extreme Isolation of Antarctica—Is This Enough to Modulate an “Allergic” Sensitization?

by Matthias Feuerecker, Claudia Strewe, Martina Aumayr, Tim Heitland, Ulrich Limper, Brian Crucian, Sarah Baatout and Alexander Choukér

Biomedicines 2022, 10(2), 448; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10020448 - 15 Feb 2022

Cited by 2 | Viewed by 2353

Abstract

(1) Background: After spending a year wintering in Antarctica, individual expedition members have reported increased or even new allergic reactions to environmental allergens after their return. (2) Methods: Blood samples from five overwintering crews were analyzed using the chip based multiplex ALEX Allergy [...] Read more.

(1) Background: After spending a year wintering in Antarctica, individual expedition members have reported increased or even new allergic reactions to environmental allergens after their return. (2) Methods: Blood samples from five overwintering crews were analyzed using the chip based multiplex ALEX Allergy Explorer (MacroArray Diagnostics GmbH, Austria). (3) Results: About one third of the 39 participants displayed specific IgEs against pollen. In most individuals, kinetics showed a reduction in the specific IgE at the time about nine months after deployment to Antarctica. Five participants had the highest specific IgE levels after returning to the “normal” world. The examination of the specific IgE relative to house dust mites and storage mites showed different kinetics. Six out of 10 had the highest specific IgE concentrations at the inner Antarctic measurement time point. These data corresponded well to the general situation in the stations. At the stations themselves, there were almost no pollen particle load, especially at Concordia. (4) Conclusions: Antarctic long-term confinement can induce an altered immune function, which is in some individuals pronounced after return to the familiar allergen environment. Future prospective studies in larger cohorts are needed to further specify these first results. Full article

(This article belongs to the Topic Translation from Microgravity Research to Earth Application)

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19 pages, 1494 KiB  

Open AccessReview

Spaceflight Stressors and Skin Health

by Wilhelmina E. Radstake, Bjorn Baselet, Sarah Baatout and Mieke Verslegers

Biomedicines 2022, 10(2), 364; https://doi.org/10.3390/biomedicines10020364 - 02 Feb 2022

Cited by 9 | Viewed by 2928

Abstract

Traveling to space puts astronauts at risk of developing serious health problems. Of particular interest is the skin, which is vitally important in protecting the body from harmful environmental factors. Although data obtained from long-duration spaceflight studies are inconsistent, there have been indications [...] Read more.

Traveling to space puts astronauts at risk of developing serious health problems. Of particular interest is the skin, which is vitally important in protecting the body from harmful environmental factors. Although data obtained from long-duration spaceflight studies are inconsistent, there have been indications of increased skin sensitivity and signs of dermal atrophy in astronauts. To better understand the effects of spaceflight stressors including microgravity, ionizing radiation and psychological stress on the skin, researchers have turned to in vitro and in vivo simulation models mimicking certain aspects of the spaceflight environment. In this review, we provide an overview of these simulation models and highlight studies that have improved our understanding on the effect of simulation spaceflight stressors on skin function. Data show that all aforementioned spaceflight stressors can affect skin health. Nevertheless, there remains a knowledge gap regarding how different spaceflight stressors in combination may interact and affect skin health. In future, efforts should be made to better simulate the spaceflight environment and reduce uncertainties related to long-duration spaceflight health effects. Full article

(This article belongs to the Topic Translation from Microgravity Research to Earth Application)

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25 pages, 940 KiB  

Open AccessReview

Dissociation of Bone Resorption and Formation in Spaceflight and Simulated Microgravity: Potential Role of Myokines and Osteokines?

by Patrick Lau, Laurence Vico and Jörn Rittweger

Biomedicines 2022, 10(2), 342; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10020342 - 01 Feb 2022

Cited by 13 | Viewed by 4042

Abstract

The dissociation of bone formation and resorption is an important physiological process during spaceflight. It also occurs during local skeletal unloading or immobilization, such as in people with neuromuscular disorders or those who are on bed rest. Under these conditions, the physiological systems [...] Read more.

The dissociation of bone formation and resorption is an important physiological process during spaceflight. It also occurs during local skeletal unloading or immobilization, such as in people with neuromuscular disorders or those who are on bed rest. Under these conditions, the physiological systems of the human body are perturbed down to the cellular level. Through the absence of mechanical stimuli, the musculoskeletal system and, predominantly, the postural skeletal muscles are largely affected. Despite in-flight exercise countermeasures, muscle wasting and bone loss occur, which are associated with spaceflight duration. Nevertheless, countermeasures can be effective, especially by preventing muscle wasting to rescue both postural and dynamic as well as muscle performance. Thus far, it is largely unknown how changes in bone microarchitecture evolve over the long term in the absence of a gravity vector and whether bone loss incurred in space or following the return to the Earth fully recovers or partly persists. In this review, we highlight the different mechanisms and factors that regulate the humoral crosstalk between the muscle and the bone. Further we focus on the interplay between currently known myokines and osteokines and their mutual regulation. Full article

(This article belongs to the Topic Translation from Microgravity Research to Earth Application)

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21 pages, 4487 KiB  

Open AccessArticle

Retrograde Analysis of Calcium Signaling by CaMPARI2 Shows Cytosolic Calcium in Chondrocytes Is Unaffected by Parabolic Flights

by Andreas Hammer, Geraldine Cerretti, Dario A. Ricciardi, David Schiffmann, Simon Maranda, Raphael Kummer, Christoph Zumbühl, Karin F. Rattenbacher-Kiser, Silvan von Arx, Sebastian Ammann, Frederic Strobl, Rayene Berkane, Alexandra Stolz, Ernst H. K. Stelzer, Marcel Egli, Enrico Schleiff, Simon L. Wuest and Maik Böhmer

Biomedicines 2022, 10(1), 138; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10010138 - 08 Jan 2022

Cited by 3 | Viewed by 4694

Abstract

Calcium (Ca²⁺) elevation is an essential secondary messenger in many cellular processes, including disease progression and adaptation to external stimuli, e.g., gravitational load. Therefore, mapping and quantifying Ca²⁺ signaling with a high spatiotemporal resolution is a key challenge. However, particularly [...] Read more.

Calcium (Ca²⁺) elevation is an essential secondary messenger in many cellular processes, including disease progression and adaptation to external stimuli, e.g., gravitational load. Therefore, mapping and quantifying Ca²⁺ signaling with a high spatiotemporal resolution is a key challenge. However, particularly on microgravity platforms, experiment time is limited, allowing only a small number of replicates. Furthermore, experiment hardware is exposed to changes in gravity levels, causing experimental artifacts unless appropriately controlled. We introduce a new experimental setup based on the fluorescent Ca²⁺ reporter CaMPARI2, onboard LED arrays, and subsequent microscopic analysis on the ground. This setup allows for higher throughput and accuracy due to its retrograde nature. The excellent performance of CaMPARI2 was demonstrated with human chondrocytes during the 75th ESA parabolic flight campaign. CaMPARI2 revealed a strong Ca²⁺ response triggered by histamine but was not affected by the alternating gravitational load of a parabolic flight. Full article

(This article belongs to the Topic Translation from Microgravity Research to Earth Application)

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29 pages, 1653 KiB  

Open AccessReview

The Cardiovascular System in Space: Focus on In Vivo and In Vitro Studies

by Ronni Baran, Shannon Marchal, Sebastian Garcia Campos, Emil Rehnberg, Kevin Tabury, Bjorn Baselet, Markus Wehland, Daniela Grimm and Sarah Baatout

Biomedicines 2022, 10(1), 59; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10010059 - 28 Dec 2021

Cited by 39 | Viewed by 6619

Abstract

On Earth, humans are subjected to a gravitational force that has been an important determinant in human evolution and function. During spaceflight, astronauts are subjected to several hazards including a prolonged state of microgravity that induces a myriad of physiological adaptations leading to [...] Read more.

On Earth, humans are subjected to a gravitational force that has been an important determinant in human evolution and function. During spaceflight, astronauts are subjected to several hazards including a prolonged state of microgravity that induces a myriad of physiological adaptations leading to orthostatic intolerance. This review summarises all known cardiovascular diseases related to human spaceflight and focusses on the cardiovascular changes related to human spaceflight (in vivo) as well as cellular and molecular changes (in vitro). Upon entering microgravity, cephalad fluid shift occurs and increases the stroke volume (35–46%) and cardiac output (18–41%). Despite this increase, astronauts enter a state of hypovolemia (10–15% decrease in blood volume). The absence of orthostatic pressure and a decrease in arterial pressures reduces the workload of the heart and is believed to be the underlying mechanism for the development of cardiac atrophy in space. Cellular and molecular changes include altered cell shape and endothelial dysfunction through suppressed cellular proliferation as well as increased cell apoptosis and oxidative stress. Human spaceflight is associated with several cardiovascular risk factors. Through the use of microgravity platforms, multiple physiological changes can be studied and stimulate the development of appropriate tools and countermeasures for future human spaceflight missions in low Earth orbit and beyond. Full article

(This article belongs to the Topic Translation from Microgravity Research to Earth Application)

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28 pages, 20206 KiB  

Open AccessReview

Cancer Studies under Space Conditions: Finding Answers Abroad

by José Luis Cortés-Sánchez, Jonas Callant, Marcus Krüger, Jayashree Sahana, Armin Kraus, Bjorn Baselet, Manfred Infanger, Sarah Baatout and Daniela Grimm

Biomedicines 2022, 10(1), 25; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10010025 - 23 Dec 2021

Cited by 12 | Viewed by 5047

Abstract

In this review article, we discuss the current state of knowledge in cancer research under real and simulated microgravity conditions and point out further research directions in this field. Outer space is an extremely hostile environment for human life, with radiation, microgravity, and [...] Read more.

In this review article, we discuss the current state of knowledge in cancer research under real and simulated microgravity conditions and point out further research directions in this field. Outer space is an extremely hostile environment for human life, with radiation, microgravity, and vacuum posing significant hazards. Although the risk for cancer in astronauts is not clear, microgravity plays a thought-provoking role in the carcinogenesis of normal and cancer cells, causing such effects as multicellular spheroid formation, cytoskeleton rearrangement, alteration of gene expression and protein synthesis, and apoptosis. Furthermore, deleterious effects of radiation on cells seem to be accentuated under microgravity. Ground-based facilities have been used to study microgravity effects in addition to laborious experiments during parabolic flights or on space stations. Some potential ‘gravisensors’ have already been detected, and further identification of these mechanisms of mechanosensitivity could open up ways for therapeutic influence on cancer growth and apoptosis. These novel findings may help to find new effective cancer treatments and to provide health protection for humans on future long-term spaceflights and exploration of outer space. Full article

(This article belongs to the Topic Translation from Microgravity Research to Earth Application)

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25 pages, 6713 KiB  

Open AccessArticle

Simulated Microgravity Subtlety Changes Monoamine Function across the Rat Brain

by Alexandra Gros, Léandre Lavenu, Jean-Luc Morel and Philippe De Deurwaerdère

Int. J. Mol. Sci. 2021, 22(21), 11759; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222111759 - 29 Oct 2021

Cited by 5 | Viewed by 2299

Abstract

Microgravity, one of the conditions faced by astronauts during spaceflights, triggers brain adaptive responses that could have noxious consequences on behaviors. Although monoaminergic systems, which include noradrenaline (NA), dopamine (DA), and serotonin (5-HT), are widespread neuromodulatory systems involved in adaptive behaviors, the influence [...] Read more.

Microgravity, one of the conditions faced by astronauts during spaceflights, triggers brain adaptive responses that could have noxious consequences on behaviors. Although monoaminergic systems, which include noradrenaline (NA), dopamine (DA), and serotonin (5-HT), are widespread neuromodulatory systems involved in adaptive behaviors, the influence of microgravity on these systems is poorly documented. Using a model of simulated microgravity (SMG) during a short period in Long Evans male rats, we studied the distribution of monoamines in thirty brain regions belonging to vegetative, mood, motor, and cognitive networks. SMG modified NA and/or DA tissue contents along some brain regions belonging to the vestibular/motor systems (inferior olive, red nucleus, cerebellum, somatosensorily cortex, substantia nigra, and shell of the nucleus accumbens). DA and 5-HT contents were reduced in the prelimbic cortex, the only brain area exhibiting changes for 5-HT content. However, the number of correlations of one index of the 5-HT metabolism (ratio of metabolite and 5-HT) alone or in interaction with the DA metabolism was dramatically increased between brain regions. It is suggested that SMG, by mobilizing vestibular/motor systems, promotes in these systems early, restricted changes of NA and DA functions that are associated with a high reorganization of monoaminergic systems, notably 5-HT. Full article

(This article belongs to the Topic Translation from Microgravity Research to Earth Application)

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20 pages, 9753 KiB  

Open AccessArticle

Collagen XV Promotes ER Stress-Induced Inflammation through Activating Integrin β1/FAK Signaling Pathway and M1 Macrophage Polarization in Adipose Tissue

by Changxing Li, Yuexia Liu, Yizhou Li, Ruiqing Tai, Zhuwen Sun, Qiong Wu, Yongnian Liu and Chao Sun

Int. J. Mol. Sci. 2021, 22(18), 9997; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22189997 - 16 Sep 2021

Cited by 14 | Viewed by 3511

Abstract

Collagen XV (Col XV), a basement membrane (BM) component, is highly expressed in adipose tissue, and studies have found that Col XV is related to extracellular matrix (ECM) remodeling involving in adipose tissue fibrosis and inflammation. Furthermore, the ECM is essential for maintaining [...] Read more.

Collagen XV (Col XV), a basement membrane (BM) component, is highly expressed in adipose tissue, and studies have found that Col XV is related to extracellular matrix (ECM) remodeling involving in adipose tissue fibrosis and inflammation. Furthermore, the ECM is essential for maintaining normal development and tissue function. In this study, we found that Col XV is related to the endoplasmic reticulum stress (ERS) and inflammation of adipose tissue. Moreover, we found that overexpression of Col XV in mice could cause macrophages to infiltrate white adipose tissue (iWAT). At the same time, the expression of the ERS sensor IRE1α (Inositol-Requiring Enzyme-1α) was significantly up-regulated, which intensified the inflammation of adipose tissue and the polarization of M1 macrophages after the overexpression of Col XV in mice. In addition, after overexpression of Col XV, the intracellular Ca²⁺ concentration was significantly increased. Using focal adhesion kinase (FAK) inhibitor PF573228, we found that PF-573228 inhibited the phosphorylation of FAK and reversed the upward trend of Col XV-induced protein expression levels of IRE1α, C/EBP-homologous protein (CHOP), and 78 kDa glucose-regulated protein (GRP78). After treatment with IRE1α inhibitor STF-083010, the results showed that the expression of adipocyte inflammation-related genes interleukin 6 (IL-6) and tumor necrosis factor α (TNFα) significantly were decreased. Our results demonstrate that Col XV induces ER-stress in adipocytes by activating the Integrinβ1/FAK pathway and disrupting the intracellular Ca²⁺ balance. At the same time, Col XV regulates the inflammation induced by ER stress in adipocytes by promoting IRE1α/XBP1 (X-Box binding protein 1) signaling. Our study provides new ideas for solving the problems of adipose tissue metabolism disorders caused by abnormal accumulation of ECM. Full article

(This article belongs to the Topic Translation from Microgravity Research to Earth Application)

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18 pages, 2403 KiB  

Open AccessArticle

The Effects of Simulated Microgravity on Macrophage Phenotype

by Christopher Ludtka, Erika Moore and Josephine B. Allen

Biomedicines 2021, 9(9), 1205; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines9091205 - 12 Sep 2021

Cited by 11 | Viewed by 3112

Abstract

The effects of spaceflight, including prolonged exposure to microgravity, can have significant effects on the immune system and human health. Altered immune cell function can lead to adverse health events, though precisely how and to what extent a microgravity environment impacts these cells [...] Read more.

The effects of spaceflight, including prolonged exposure to microgravity, can have significant effects on the immune system and human health. Altered immune cell function can lead to adverse health events, though precisely how and to what extent a microgravity environment impacts these cells remains uncertain. Macrophages, a key immune cell, effect the inflammatory response as well as tissue remodeling and repair. Specifically, macrophage function can be dictated by phenotype that can exist between spectrums of M0 macrophage: the classically activated, pro-inflammatory M1, and the alternatively activated, pro-healing M2 phenotypes. This work assesses the effects of simulated microgravity via clinorotation on M0, M1, and M2 macrophage phenotypes. We focus on phenotypic, inflammatory, and angiogenic gene and protein expression. Our results show that across all three phenotypes, microgravity results in a decrease in TNF-α expression and an increase in IL-12 and VEGF expression. IL-10 was also significantly increased in M1 and M2, but not M0 macrophages. The phenotypic cytokine expression profiles observed may be related to specific gravisensitive signal transduction pathways previously implicated in microgravity regulation of macrophage gene and protein expression. Our results highlight the far-reaching effects that simulated microgravity has on macrophage function and provides insight into macrophage phenotypic function in microgravity. Full article

(This article belongs to the Topic Translation from Microgravity Research to Earth Application)

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