Atormac
Neurology India
menu-bar5 Open access journal indexed with Index Medicus
  Users online: 5214  
 Home | Login 
About Editorial board Articlesmenu-bullet NSI Publicationsmenu-bullet Search Instructions Online Submission Subscribe Videos Etcetera Contact
  Navigate Here 
 Search
 
  
 Resource Links
  »  Similar in PUBMED
 »  Search Pubmed for
 »  Search in Google Scholar for
 »Related articles
  »  Article in PDF (1,534 KB)
  »  Citation Manager
  »  Access Statistics
  »  Reader Comments
  »  Email Alert *
  »  Add to My List *
* Registration required (free)  

 
  In this Article
 »  Abstract
 »  Microgravity and...
 »  Historical Persp...
 »  Investigating Ce...
 »  Microgravity and...
 »  Microgravity Eff...
 »  Microgravity Eff...
 » Conclusion
 »  References
 »  Article Figures

 Article Access Statistics
    Viewed124    
    Printed6    
    Emailed0    
    PDF Downloaded6    
    Comments [Add]    

Recommend this journal

 


 
Table of Contents    
GUEST COMMENTARY
Year : 2019  |  Volume : 67  |  Issue : 3  |  Page : 684-691

Cellular changes in the nervous system when exposed to gravitational variation


Department of Biology, Texas Southern University, Houston, Texas, USA

Date of Web Publication23-Jul-2019

Correspondence Address:
Dr. Alamelu Sundaresan
Department of Biology, Texas Southern University, 3001 Cleburne Street, Houston, Texas -77004
USA
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0028-3886.263169

Rights and Permissions

 » Abstract 


This review discusses the past and recent findings on how changes in gravity affect cellular and subcellular parameters of the human nervous system and the implementation of cell and tissue models of nervous tissue on space biology. In order to prepare for long duration space exploration, a focus on space life sciences research is critical. Such research not only improves our knowledge of the basic biological processes but also elucidates the mechanisms and treatment of various earthly medical conditions. However, the study of living organisms in space poses many challenges that may be negligible or nonexistent in ground-based research. In recent years, with an increase in the number of spaceflights, extended periods of stay of astronauts on the International Space station and the imminent possibility of future long term deep space exploration missions, there is a great deal of attention focused on the effects induced by altered gravitation on the human body, and in particular, on bone, skeletal muscle, immunity and brain function. The aim of this review is to collate, encapsulate and examine the effects of altered gravity on neuronal cell structure and function that have been established from data obtained during experiments performed in real microgravity and simulated microgravity like conditions.


Keywords: Microgravity analogue, microgravity, neuroglia, neurology, sensorimotor
Key Message: The effects induced by altered gravitation on the human body, and in particular, on bone, skeletal muscle, immunity and brain function are reviewed. The cellular and subcellular parameters of the human nervous system and the implementation of cell and tissue models of the nervous tissue on space biology are also discussed.


How to cite this article:
Mann V, Sundaresan A, Chaganti M. Cellular changes in the nervous system when exposed to gravitational variation. Neurol India 2019;67:684-91

How to cite this URL:
Mann V, Sundaresan A, Chaganti M. Cellular changes in the nervous system when exposed to gravitational variation. Neurol India [serial online] 2019 [cited 2019 Aug 21];67:684-91. Available from: http://www.neurologyindia.com/text.asp?2019/67/3/684/263169




As life evolved on Earth, a myriad of changes in the physical and chemical factors invoked adaptations and selections that induced the convoluted evolutionary pressures. Earth's gravitational force has been constant in direction and magnitude since the formation of the planet.[1],[2] All living beings including animals, plants and humans, for this reason, have advanced to contrive with and rely upon gravity. From time immemorial, all living organisms adapted their cellular and operating functions to gravity characteristic of our planet Earth.

Simulated microgravity is established on the premise that absence of weight load is realized, similarly to nullification of sedimentation during weightlessness (0 g).[3] In simulated microgravity circumstances, complete weightlessness is never entirely reached, as weak residual acceleration forces are still active. Ground-based devices such as the random positioning machine, the rotating wall vessel and the fast-rotating clinostats have successfully replicated microgravity responses.[4] However, these devices generally seem to underestimate the effects observed in real microgravity during spaceflights.[5] Altered gravity conditions like hypo- and hyper- gravity have had differential effects on living beings at various levels of organization, ranging from changes in the biophysical properties of single cells to the intact nervous system.

It is important to incorporate the different findings into a consistent model to gain insights into how the components of the nervous system interact as a response to the short- and long-term gravitational variation. With emphasis on future space travel, including space tourism, planned long-term manned missions to Moon, Mars and interplanetary explorations, it is imperative to understand the impact of altered gravity on the nervous system and the gravity-perceiving systems, which determines movement, cognition, and survival.[6]

Studies of astronauts participating in space missions on the International Space Station (ISS) have demonstrated spaceflight-induced ocular changes such as choroidal folds, optic disk edema, globe flattening, and hyperoptic shifts.[7] In vitro studies on different types of human renal cortical cells or mouse MC3T3 osteoblasts, hFOB human fetal osteoblasts, in space or on microgravity simulating devices, have demonstrated significant changes in gene expression patterns,[8],[9],[10] increased apoptosis [ML1 follicular thyroid cancer cells, glial cells, MDA-MB231 breast cancer cells and human lymphocytes (Jurkat)][11],[12],[13],[14] and induction of autophagy (human umbilical vein endothelial cells, HEK293 cells),[15],[16] as well as changes in differentiation (FTC-133 follicular thyroid cancer cells),[17] migration, cell adhesion, extracellular matrix composition (ML1 cells)[11] and alterations in the cytoskeleton (FTC-133 cells, A431 epidermoid carcinoma cells).[18],[19] The nervous system controls muscle contraction permitting the body to withstand the gravitational force and manage locomotor patterns and reflexes during the evolutionary shift from aqueous to terrestrial life.[20] One of the fundamental circuits within the central nervous system (CNS) to control muscle contraction is the monosynaptic reflex arch. The monosynaptic reflex arc, which is an important circuit within the central nervous system, responds to an external stimulus, which leads to fast muscle contractions. The measure of muscle contraction depends on the size of the sensory input.[21]

In order to maintain a simple posture or movement for mobility of the terrestrial life, the nervous system processes sensory information from the vestibular, visual systems and proprioception. These sensorimotor competencies are crucial for life.[22],[23],[24],[25],[26] Further, there are modifications in the neuromuscular system underlying health-related changes that open up many questions on how the variation of gravity influences the nervous system. Countermeasures to re-establish homeostatic states within the human body have begun, but the pathophysiologic mechanisms of altered gravity on the neurologic system are still obscure. Here, we recapitulate the current knowledge of neurologic adjustments encountered or expected from space exposure, the most unconventional environmental pressure to affect the human species.


 » Microgravity and Cellular Behavior Top


The direct effects of microgravity on various tissues of the musculoskeletal, cardiopulmonary, immune, nervous and vestibular systems are well documented.[27] Nevertheless, at a cellular level, these effects are largely indirect and are moderated through the modification of a complex variety of physicochemical affects, such as hemodynamic and hydrostatic pressure, fluid shear stress, three-dimensional tissue stress, mass transport, and permeability. These direct and indirect effects can be sensed by cells in many ways, for example, via membrane-bound receptors and ion channels, primary cilia, cell shape, cytoskeletal and membrane structure changes.[28] Cell's morphological polarity determines its behavior. For instance, non-polarized cells are more likely to undergo apoptosis.[28],[29] Depending on the origin of cells, apoptosis may be increased or decreased and it may be affected when the cell cytoskeleton is disorganized.[29] An increase in cell apoptosis is a significant consequence of the changes in cell structure and function that occur in microgravity.[30] Microgravity has effects on both cell shape and cytoskeleton.[31]


 » Historical Perspective Top


For long, it has been assumed that cells are too insignificant in mass to be affected by microgravity. But in reality, space travel, and in particular microgravity, does affect cells. Multiple experiments from the past three decades have demonstrated that spaceflight significantly changes the morphology and function of human and microbial cells in culture.[32],[33],[34],[35],[36],[37],[38],[39],[40] The history of gravitational cell biology can be traced back to the nineteenth century,[41] when Julius Sachs (1863), Charles Darwin (1880), and Wilhelm Pfeiffer (1904) investigated the influence of gravity on plants, with the downward orientation of root caps.[41] In the 1960s, early satellites had some bacterial, plant, and animal experiments aboard. However, these experiments had logistical and technical constrains which were overcome by the Skylab platform that allowed scientists to embark on a new era in microgravity research.

These early studies set the stage for investigation of the effects of microgravity on red blood cell shape, bone loss, muscle deconditioning, metabolic changes, and immune performance.[42] Following the Skylab based research, the Shuttle era opened new vistas for scientific experiments. It was during this time, and in the follow-up studies on the Shuttle program that some of the key findings with regard to mammalian cells in space took place. These findings include: (1) Inhibition of lymphocyte activation, cytokine production, and locomotion;[43],[44],[45] (2) interference with transmembrane signaling;[46],[47] (3) changes in metabolism;[48],[49],[50] and (4) tissue morphogenesis.[51],[52]


 » Investigating Cells in Space Top


Our experimental methods for investigating the effects of microgravity on biological systems are limited. Space is the most reliable environment in which to conduct these experiments; however, there is currently limited access to the space-flight research platform. In the absence of routine spaceflight opportunities, there are several approaches that provide brief periods of analogue conditions; namely, drop towers, parabolic flights, suborbital missions, supported by ground-based model systems for simulated microgravity such as clinorotation, rotating wall vessels, three-dimensional (3D)-random positioning machines and diamagnetic levitation.[53] [Figure 1].
Figure 1: Microgravity analogue systems applicable to mammalian and microbial cells. Analogues are systems and/or devices that mimic some of the characteristics of microgravity. Since micro-gravity opportunities are infrequent, we rely on ground-based analogues to initiate investigations, profile the actual space-flight experiment, and design cell culture equipment for flight. There are at least eight analogue systems used for microbial and human cells, and tissue specimens. Four of these systems are represented here. (Open Source: Reprinted with permission)

Click here to view



 » Microgravity and the Nervous System Top


The nervous system is the master controlling and communicating system of the body. It is a network of neurons and fibers which transmits nerve impulses between parts of the body. Cells communicate via electrical and chemical signals. The nervous system originates from the neural tube and neural crest, formed from the ectoderm. The neural tube becomes the central nervous system. Neuroepithelial cells of the neural tube proliferate into a number of cells needed for development.

Neuroblasts become amitotic and migrate, and later sprout axons to connect with targets and become neurons. The neuronal plasticity of the adult brain depends on the correct timing and expression of primordial cell proliferation and migration, before entering into their differentiation processes. The gravity on earth is responsible for maintaining a conditioning fluctuation state of cells and their organelles, which is lost in weightless conditions.[54]

The Neurolab flight was the third space shuttle mission dedicated to life science research, but it was the first mission to focus distinctly on how the neurological system responds to the challenges of space flight. During the early years of the National Aeronautics and Space Administration's (NASA's) manned space flight program, efforts in the life sciences were driven by the operational medicine and biomedical support of short duration ventures such as the Mercury and Gemini missions. During these flights, according to the NASA literature, no significant problems arose regarding sensory system function. However, during the Apollo missions, a number of astronauts reported mild-to-severe motion sickness, and in the early 1970's, NASA initiated studies of the illness. More recently, attention has been devoted to other physiological and behavioral changes that occur as a result of space flight. The data obtained throughout the Neurolab project starting in 1990's till 2003, showed that the absence of gravity had limited, and reversible, effects on the functional capabilities of the mature human brain.[54]

The Neurolab experiments have also affirmed that microgravity influences not only the sensory input, but also the brain integrating functions, and consequently its motor output. In the microgravity environment, the balance between the senses needs to be re-organized, e.g., the limbs are weightless in space, and this implies that some movements have to be re-calibrated.[54] The Neurolab experiments, performed on animal models during their development, have suggested that microgravity affects nervous system development, to induce long-lasting modifications, compared to this development on Earth. Also, the 30-day flight experiments performed on the Russian Bion-M1 biosatellite, using male mice, revealed that after the return from the 30-day spaceflight, the mice were markedly less active compared to the control groups that had remained on Earth, and they displayed signs of pronounced inadaptation to Earth's gravity.[55] Moreover, the expression of genes involved in dopamine synthesis and degradation was reduced, although this did not modify the expression of the main genes of serotonin metabolism and signaling. It did, however, reduced 5 hydroxy-tryptamine 2A (5-HT2A) receptor gene expression in the hypothalamus. For these reasons, these alterations to the dopamine system might also contribute to spaceflight-induced neuromotor impairment that has been detected in both humans and mice.[56]

Even though there is ample evidence supporting the hypothesis that exposure to microgravity has contrasting effects on the nervous system, in some cases it has been shown that microgravity does not disturb cell differentiation and tissue assembly.[57],[58],[59] In other cases, microgravity appears to strongly alter cell morphology and function,[60],[61],[62] or to even improve stem cell differentiation into neurons.[63],[64],[65] A three-dimensional (3D) in-vitro neuroglial co-culture model was proposed by Morabito and co-workers (2015), using GL15 and SH-SY5Y cells, which are astrocyte-like and neuronal-like cells, respectively. The cells grown as co-culture under simulated microgravity, as compared to cells grown as static monolayers, showed a significant increase in the expression of some differentiation-specific markers, such as glial fibrillary acidic protein (GFAP) and S100B in the glial cells, and growth associated protein 43 (GAP43) in the pseudo-neurons. Also, both of these cell types showed an increased expression of neural cell adhesion molecule (N-CAM) and conexin 43 (Cx43), as a result of increased functional cell-cell interactions.[65]

Studies of astronauts participating in missions on the International Space Station have shown prominent adverse outcomes in visual function.[7] The adverse outcomes were observed in astronauts after a long-term spaceflight and it has been hypothesized that these visual changes are connected to cephalad fluid shifts, intracranial pressure and optic nerve sheath compartment syndrome, as a consequence of prolonged microgravity exposure.[7],[66],[67] Simulated microgravity induces significant alterations in the F-actin-cytoskeleton and cytoskeleton-related proteins of human retinal pigment epithelial cell line (ARPE-19), in addition to changes in the cell growth behavior and gene expression patterns involved in cell structure, growth, shape, migration, adhesion and angiogenesis.[68]


 » Microgravity Effects on Neuronal Membrane Top


The cell membrane lipid bilayer properties are known to respond to various changing conditions such as temperature,[69] deformation,[70] pH,[71] specific ions,[72] and gravity.[73] Also, changes are seen in membrane structure, composition, bi-leaflet organization, lipid rafts, and in association with the cytoskeleton [Figure 2]. These changes are presumed to be due to the initial response of the cell, minimizing its surface area-to-volume ratio. From experiments with unicellular organisms [74] and various cell types, such as the immune cells [75] and the neuronal cells,[76] it is well established that single cells react to changes in gravity even though they do not have dedicated gravity-sensing structures. Neurons can change their membrane potential in order to communicate. This ability is based on the activity of the integrated membrane proteins as ion channels and ion pumps. The physicochemical state of the lipid membrane can directly modify the function of membrane proteins.[77],[78] In experiments conducted in the non-microgravity environment (1g), it was shown that with decrease in membrane fluidity, the closed-state probability of nicotinic acetylcholine receptors (nAChRs) increased.[79]
Figure 2: Cytoskeletal staining of F-actin microfilaments and quantitative alterations of genes of cytoskeletal proteins in ARPE-19 cells exposed to simulated microgravity. (a-h) CLSM after a 5d-exposure (c and d) and a 10d-exposure (g and h) on the RPM and their corresponding 1g-control cells (a,b,e and f). Inserts of (a and b) show freshly established ARPE-19 cells with normal cytoskeleton at T0 (1g) and 3d (1g), respectively. Red staining: TRITC-phalloidin to visualize the F-actin; blue staining: DAPI labeling of nucleus. White arrowheads indicate region of interest. Scale bar: 20 μm. (I-L) Gene expression analyses of cytoskeletal genes assessed by qRT-PCR. After 5d and 10d 1g-control, RPM-adherent (AD) cells, and RPM-multicellular spheroids (MCS) were analyzed for their relative expression levels of (i) ACTB; (j) TUBB; (k) VIM; (l) KRT8 correlated to 18SrRNA. The 5d and 10d 1g-controls were set to 100% * = P < 0.05. (Open Source: Reprinted with permission)

Click here to view


These nAChRs are major players in the sensorimotor system as they are located in the motor end plates that form the interface between the neuronal system and the muscles. Experiments performed in micro- and hyper-gravity models using artificial asolectin vesicles and human neuronal SH-SY5Y cells showed a significant increase in the membrane fluidity in microgravity and its decrease in hyper-gravity.[80]


 » Microgravity Effects on Ion Channels and the Electrophysiological Properties of Neurons Top


Historically, we have known about mechanosensitive channels and their ability to inform the cells of the environment with respect to hydrodynamic/fluid shear, physical impact, stretching, and perhaps even microgravity itself. These channels are responsible for modulation of ion flow in and out of the cell, and as a consequence, can modulate a number of cascading activities beyond that.[81],[82] Ion channels are pore forming proteins that allow ions to pass through the channel pore. These ion channels are crucial for neuronal communication. Neuronal ion channel activation occurs in either a voltage-gated or a ligand-gated manner. Ion channels play crucial roles in neuronal signal processing [83],[84],[85] and plasticity.[86],[87],[88] The physiological function of many ion channels that have been identified to be mechanosensitive is still unknown.[89]

Thus far, in microgravity research, no native ion channel proteins have been used. Instead, pore-forming peptides, which can be used as ion channel analogs, have been employed to study the ion channel parameters as open- and closed-state probability. Microgravity experiments have showed that the open-state probability of porin channels from  Escherichia More Details coli is significantly decreased, whereas in hyper-gravity, it is increased.[90] Additionally, alamethicin, an artificial pore-forming peptide from Trichodermaviride, manifested decreased activity in microgravity and hyper-gravity.[91],[92] Moreover, in parabolic flight experiments, native oocytes from Xenopus laevis, as well as oocytes that overexpress epithelial sodium channels (ENaC), demonstrated reduced membrane conductivity under microgravity and increased conductivity under hyper- gravity.[93],[94] With the onset of a different gravity condition, the open-state probability is changed, returning to normal as soon as the experiment returns to the normal 1 g gravity. Gravity influences the velocity of propagating waves in the excitable media of neuronal tissue.[95] Other experiments have shown that electrical properties of neurons are not affected by microgravity, and cell characterization by immunostaining shows a normal neuronal phenotype.[96] In contrast to these findings, Ranjan and colleagues (2014) observed that in rats exposed to simulated microgravity, some areas of the active zone of the cornu Ammonis 1(CA1) hippocampal neurons significantly decreased, while dendritic arborization and the number of spines significantly increased.[97] A stable resting membrane potential is essential for neurons to communicate, and this can be modulated by changing the activity of relevant ion channels. Experiments on the parabolic flight during microgravity phase have shown significant depolarization (3mV) of the resting potential of human neuronal cells, and vice versa, in hyper-gravity.[3] Another microgravity analogue model obtained by drop tower, showed that the rate of action potentials triggered by the spontaneously active leech neurons is significantly increased.[98] The action potential kinetics are gravity dependent as well. The action potential propagation velocity on the axonal level is decreased in microgravity and is increased in hyper-gravity, which was demonstrated in parabolic flight missions in vitro in isolated earthworm axons and isolated rat axons, and in vivo in intact earthworms.[98] All of these changes are fast and fully reversible.


 » Conclusion Top


Microgravity provides environmental characteristics that are difficult to obtain on Earth. Using extreme conditions that modify the physical force environment to investigate life processes affords opportunities for the discovery and development of applications that significantly enhance research. The 3D co-culture of neuronal and glial cells in rotating bioreactors can provide in-vitro models for physiological and pathophysiological investigations also in still unexplored fields, such as the development of the nervous system.

Till date, many in vitro and in vivo experiments have been conducted to investigate the effects of micro- and hyper-gravity on neuronal tissue. From molecular-to-cellular-to-system levels (both neuromuscular and nervous), all have shown to adapt to changes in the gravity conditions.[99] The new International Space Station strategy affords multiple experiments and real-time modifications. In combination with the ongoing improvements in flight hardware that incorporate experimental flexibility, modularity, and advanced capabilities to enable a broad range of biological experiments, these experiments are enhancing the potential for innovative biomedical and biotechnological applications. Additionally, valuable microgravity analogues can be used on the ground to profile experiments for spaceflight to identify specific biological characteristics to be observed in microgravity.[100] Countermeasures such as vibration treatment, sensorimotor training, and artificial gravity have been applied to counter the deleterious effects of changes in gravity.[101]

Microgravity, thus, affords a new window through which one may observe life processes. In the short time that we have studied microgravity, it is apparent that terrestrial life responds to the physical change in gravity by altering gene expression, inhibiting cellular movement, promoting differentiation, and inducing profound morphological changes. Cells adapt, and most survive the transition. In experiments conducted over a short duration in the microgravity environment, the changes are genuinely phenotypical, and therefore, resolve when the gravity status is returned to 1g. Microgravity is thus a probe which, as with other physical stresses, can reveal novel mechanisms that are fundamental to the cell processes, disease processes, and the adaptation of living systems to changes in physical forces. As astronauts travel to Mars and deeper outer space, they will live in the absence of gravity for extended periods of time with transition between weightlessness, isolation, outer space radiation and altered planetary gravitational forces during various phases of the mission. Considering the gravity dependency of the nervous system, further research and countermeasure developments will be necessary to assure a safe space travel and Earth return in the future.[101]

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 » References Top

1.
Mariggiò MA, FanòIllic G. The effects of simulated microgravity on the human nervous system: The proposal of a three-dimensional glia-neuron co-culture cell model. Science Proceedings 2015;2:e892.  Back to cited text no. 1
    
2.
Montmerle T, Augereau JC, Chaussidon M, Gounelle M, Marty B, Morbidelli A. Solar system formation and early evolution: The first 100 million years. In: Gargaud M, Claeys P, López-García P, Martin H, Montmerle, T, Pascal R, Reisse J (Editors) From Suns to Life: A Chronological Approach to the History of Life on Earth. Springer, New York 2006;98:39-95.  Back to cited text no. 2
    
3.
Schaffhauser DF, Andrini O, Ghezzi C, Forster IC, Franco-Obregón A, Egli M, Dittrich PS. Microfluidic platform for electrophysiological studies on Xenopus Laevis oocytes under varying gravity levels. Lab Chip 2011;11:3471-8.  Back to cited text no. 3
    
4.
Grimm D, Wehland M, Pietsch J, Aleshcheva G, Wise P, van Loon J, et al. Growing tissues in real and simulated microgravity: New methods for tissue engineering. Tissue Eng Part B Rev 2014;20:555-66.  Back to cited text no. 4
    
5.
Wuest SL, Richard S, Kopp S, Grimm D, Egli M. Simulated microgravity: Critical review on the use of random positioning machines for mammalian cell culture. Biomed Res Int 2015; 2015:1-8. Available from: http://dx.doi.org/10.1155/2015/971474. [Last accessed on 2019 May 02].  Back to cited text no. 5
    
6.
Lister A, Rothschild LJ, editors. Evolution on Planet Earth: The Impact of the Physical Environment. Amsterdam, Boston: Academic Press; 2003. Available from: https://www.sciencedirect.com/book/9780125986557/evolution-on-planet-earth#book-description. [Last accessed on 2019 May 02].  Back to cited text no. 6
    
7.
Mader TH, Gibson CR, Pass AF, Kramer LA, Lee AG, Fogarty J, et al. Optic disc edema, globe flattening, choroidal folds, and hyperopic shifts observed in astronauts after long-duration space flight. Ophthalmology 2011;118:2058-2069.  Back to cited text no. 7
    
8.
Mann V, Grimm D, Corydon TJ, Krüger M, Wehland M, Riwaldt S, et al. Changes in human foetal osteoblasts exposed to the random positioning machine and bone construct tissue engineering. Int J Mol Sci 2019;20:1357.  Back to cited text no. 8
    
9.
Hammond TG, Lewis FC, Goodwin TJ, Linnehan RM, Wolf DA, Hire KP, et al. Gene expression in space. Nat Med 1999;5:359.  Back to cited text no. 9
    
10.
Hammer BE, Kidder LS, Williams PC, Xu WW. Magnetic levitation of mc3t3 osteoblast cells as a ground-based simulation of microgravity. Microgravity Sci Technol 2009;21:311-18.  Back to cited text no. 10
    
11.
Grimm D, Bauer J, Kossmehl P, Shakibaei M, Schoberger J, Pickenhahn H, et al. Simulated microgravity alters differentiation and increases apoptosis in human follicular thyroid carcinoma cells. FASEB J 2002;16:604-6.  Back to cited text no. 11
    
12.
Uva BM, Masini MA, Sturla M, Bruzzone F, Giuliani M, Tagliafierro G, et al. Microgravity-induced apoptosis in cultured glial cells. Eur J Histochem 2002;46:209-14.  Back to cited text no. 12
    
13.
Masiello MG, Cucina A, Proietti S, Palombo A, Coluccia P, D'Anselmi F, et al. Phenotypic switch induced by simulated microgravity on mda-mb-231 breast cancer cells. Biomed Res Int 2014;2014. DOI: Available from: http://dx.doi.org/10.1155/2014/652434. [Last accessed on 2019 May 02].  Back to cited text no. 13
    
14.
Lewis ML, Reynolds JL, Cubano LA, Hatton JP, Lawless BD, Piepmeier EH. Spaceflight alters microtubules and increases apoptosis in human lymphocytes (Jurkat). FASEB J 1998;12:1007-18.  Back to cited text no. 14
    
15.
Li CF, Sun JX, Gao Y, Shi F, Pan YK, Wang YC, et al. Clinorotation-induced autophagy via hdm2-p53-mtor pathway enhances cell migration in vascular endothelial cells. Cell Death Dis 2018;9:147.  Back to cited text no. 15
    
16.
Ryu HW, Choi SH, Namkoong S, Jang IS, Seo DH, Choi I, et al. Simulated microgravity contributes to autophagy induction by regulating amp-activated protein kinase. DNA Cell Biol 2014;33:128-35.  Back to cited text no. 16
    
17.
Ma X, Pietsch J, Wehland M, Schulz H, Saar K, Hubner N, et al. Differential gene expression profile and altered cytokine secretion of thyroid cancer cells in space. FASEB J 2014;28:813-35.  Back to cited text no. 17
    
18.
Corydon TJ, Kopp S, Wehland M, Braun M, Schutte A, Mayer T, et al. Alterations of the cytoskeleton in human cells in space proved by life-cell imaging. Sci Rep 2016;6:20043. DOI: 10.1038/srep20043.  Back to cited text no. 18
    
19.
Moes MJA, Gielen JC, Bleichrodt RJ, van Loon JJ, Christianen PCM, Boonstra J. Simulation of microgravity by magnetic levitation and random positioning: Effect on human a431 cell morphology. Microgravity Sci Technol 2011;23:249-61.  Back to cited text no. 19
    
20.
Kohn FPM, Koch C, Ritzmann R. The effect of gravity on the nervous system, into space-a journey of how humans adapt and live in microgravity. Intech Open 2018;6:88-97.  Back to cited text no. 20
    
21.
Ritzmann R, Krause A, Freyler K, Gollhofer A. Gravity and neuronal adaptation-Neurophysiology of reflexes from hypo to hyper gravity conditions. Microgravity Science and Technology 2017;29:9-18. 10.1007/s12217-016-9519-4  Back to cited text no. 21
    
22.
Margaria R, Cavagna GA. Human locomotion in sub gravity. Aerosp Med 1964;22:1140-6.  Back to cited text no. 22
    
23.
Homick JL, Reschke MF. Postural equilibrium following exposure to weightless space flight. Acta Otolaryngol 1977;83:455-64.  Back to cited text no. 23
    
24.
Paloski WH, Black FO, Reschke MF, Calkins DS, Shupert C. Vestibular ataxia following shuttle flights: Effects of microgravity on otolith-mediated sensorimotor control of posture. Am J Otol 1993;14:9-17.  Back to cited text no. 24
    
25.
Layne CS, Mulavara AP, McDonald PV, Pruett CJ, Kozlovskaya IB, Bloomberg JJ. Effect of long-duration spaceflight on postural control during self-generated perturbations. J Appl Physiol 2001;90:997-1006.  Back to cited text no. 25
    
26.
Ritzmann R, Freyler K, Weltin E, Krause A, Gollhofer A. Load dependency of postural control—kinematic and neuromuscular changes in response to over and under load conditions. PLoS One 2015;10:e0128400 DOI: 10.1371/journal.pone. 0128400  Back to cited text no. 26
    
27.
Sundaresan A, Pellis NR. Effect of spaceflight and analogue culture on mammalian and microbial cells: Novel insights into disease mechanisms. Microgravity Biotechnology/Technology Developments 2016;6:3-10.  Back to cited text no. 27
    
28.
Ingber D. In search of cellular control: Signal transduction in context. J Cell Biochem Suppl 1998;30-31:232-237.  Back to cited text no. 28
    
29.
Zahir N, Weaver VM. Death in the third dimension: Apoptosis regulation and tissue architecture. Curr Opin Genet Dev 2004;14:71-80.  Back to cited text no. 29
    
30.
Schatten H, Lewis ML, Chakrabarti A. Spaceflight and clinorotation cause cytoskeleton and mitochondria changes and increases in apoptosis in cultured cells. Acta Astronaut 2001;49:399-418.  Back to cited text no. 30
    
31.
Gaboyard S, Blanchard MP, Travo C, Viso M, Sans A, Lehouelleur J. Weightlessness affects cytoskeleton of rat utricular hair cells during maturation in vitro. Neuro Report 2002;13:2139-42.  Back to cited text no. 31
    
32.
Cogoli A. Gravitational physiology of human immune cells: A review of in vivo, ex vivo and in vitro studies. J Gravit Physiol 1996;3:1-9.  Back to cited text no. 32
    
33.
Sundaresan A, Risin D, Pellis NR. Cell growth in microgravity. In Meyers RA, Sendtko A, Henheik P (Eds.), Encyclopedia of molecular cell biology and molecular medicine. Weinheim, Germany: Wiley-VCH 2004;3:303-21.  Back to cited text no. 33
    
34.
Nickerson CA, Ott CM, Wilson JW, Ramamurthy R, Pierson DL. Microbial responses to microgravity and other low-shear environments. Microbiol Mol Biol Rev 2004;68:345-61.  Back to cited text no. 34
    
35.
Horneck G, Klaus DM, Mancinelli RL. Space microbiology. Microbiol Mol Biol Rev 2010;74:121-56.  Back to cited text no. 35
    
36.
Kim W, Tengra FK, Young Z, Shong J, Marchand N, Chan HK, et al. Effect of spaceflight on Pseudomonas aeruginosa final cell density is modulated by nutrient and oxygen availability. BMC Microbiol 2013;13:241.  Back to cited text no. 36
    
37.
Kim W, Tengra FK, Young Z, Shong J, Marchand N, Chan HK, et al. Spaceflight promotes biofilm formation by Pseudomonas aeruginosa. PLoS One 2013;8:62437. DOI: 10.1371/journal.pone. 0062437.  Back to cited text no. 37
    
38.
Ott CM, Crabbe A, Wilson JW, Barrila JB, Nickerson CA. Effect of spaceflight on microbial gene expression and virulence. In Chouker A (Ed.), Stress challenges and immunity in space Heidelberg, Germany: Springer. 2011;203-225. Available from: https://www.springer.com/in/book/9783642222719. [Last accessed on 2019 May 02].  Back to cited text no. 38
    
39.
Vunjak-Novakovic G, Searby N, Luis JD, Freed LE. Microgravity studies of cells and tissues. Ann N Y Acad Sci 2002;974,504-17.  Back to cited text no. 39
    
40.
Fitzgerald W, Chen S, Walz C, Zimmerberg J, Margolis L, Grivel JC. Immune suppression of human lymphoid tissues and cells in rotating suspension culture and onboard the International Space Station. In Vitro Cell Dev Biol Anim 2009;45:622-32.  Back to cited text no. 40
    
41.
Gargaud, M. Encyclopedia of astrobiology. In M. Gargaud et al. (Eds.). Encyclopedia of Astrobiology. New York, NY: Springer. 2011. Available from: https://www.springer.com/in/book/9783642112744. [Last accessed on 2019 May 02].  Back to cited text no. 41
    
42.
Johnston RS, Dietlein LF, Biomedical results from Skylab (Vol. SP-377). Washington, DC: NASA Government Printing Office 1977. Available from: https://ntrs.nasa.gov/search.jsp?R=19770026836. [Last accessed on 2019 May 02].  Back to cited text no. 42
    
43.
Pellis NR, Goodwin TJ, Risin D, McIntyre BW, Pizzini RP, Cooper D, et al. Changes in gravity inhibit lymphocyte locomotion through type I collagen. In Vitro Cell Dev Biol Anim 1997;33:398-405.  Back to cited text no. 43
    
44.
Cogoli A. Signal transduction in T lymphocytes in microgravity. Gravit Space Biol Bull 1997;10:5-16.  Back to cited text no. 44
    
45.
Cogoli A, Cogoli-Greuter M. Activation and proliferation of lymphocytes and other mammalian cells in microgravity. Adv Space Biol Med1997;6:33-79.  Back to cited text no. 45
    
46.
Sundaresan A, Risin D, Pellis NR. Loss of signal transduction and inhibition of lymphocyte locomotion in a ground-based model of microgravity. In Vitro Cell Dev Biol Anim 2002;38:118-122.  Back to cited text no. 46
    
47.
Nakamura K, Kuga H, Morisaki T, Baba E, Sato N, Mizumoto K, et al. Simulated microgravity culture system for a 3-D carcinoma tissue model. Biotechniques 2002;33:1068-70  Back to cited text no. 47
    
48.
Manchester JK, Chi MM, Norris B, Ferrier B, Krasnov I, Nemeth PM. Effect of microgravity on metabolic enzymes of individual muscle fibers. FASEB J1990;4:55-63.  Back to cited text no. 48
    
49.
Gao H, Liu Z, Zhang L. Secondary metabolism in simulated microgravity and space flight. Protein Cell 2011;2:858-61.  Back to cited text no. 49
    
50.
Huang B, Li DG, Huang Y, Liu CT. Effects of simulated microgravity and spaceflight on morphological differentiation and secondary metabolism of Streptomyces coelicolor A3(2). Appl Microbiol Biotechnol 2015;99:4409-22.  Back to cited text no. 50
    
51.
Unsworth BR, Lelkes PI. Growing tissues in microgravity. Nature Med 1998;4:901-7.  Back to cited text no. 51
    
52.
Freed LE, Langer R, Martin I, Pellis NR, Vunjak-Novakovic G. Tissue engineering of cartilage in space. Proc Natl Acad Sci USA 1997;94:13885-90.  Back to cited text no. 52
    
53.
Schwarzenberg M, Pippia P, Meloni MA, Cossu G, Cogoli-Greuter M, CogoliA. Signal transduction in T lymphocytes--a comparison of the data from space, the free fall machine and the random positioning machine. Adv Space Res1999;24:793-800.  Back to cited text no. 53
    
54.
Buckey JC, Homick JL, eds. Neurolab Spacelab Mission: Neuroscience Research in Space Results from the STS-90, Neurolab Spacelab Mission. NASA SP-2003-535. Houston, Texas: National Aeronautics and Space Administration Lyndon B. Johnson Space Center, 2003. Available from: https://ntrs.nasa.gov/search.jsp?R=20030068190. [Last accessed on 2019 May 02].  Back to cited text no. 54
    
55.
Andreev-Andrievskiy A, Popova A, Boyle R, Alberts J, Shenkman B, Vinogradova O, et al. Mice in Bion-M 1 space mission: Training and selection. PLoS One 2014;9:104830. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4136787/. [Last accessed on 2019 May 02].  Back to cited text no. 55
    
56.
Popova NK, Kulikov AV, Kondaurova EM, Tsybko AS, Kulikova EA, Krasnov IB, et al. Risk neurogenes for long-term spaceflight: Dopamine and serotonin brain system. Mol Neurobiol 2014;51:1443-1451.  Back to cited text no. 56
    
57.
Crestini A, Zona C, Sebastiani P, Pieri M, Caracciolo V, Malvezzi-Campeggi L, et al. Effects of simulated microgravity on the development and maturation of dissociated cortical neuron. In Vitro Cell Deve Biol—Animal 2004;40:159-65.  Back to cited text no. 57
    
58.
Husson D, Gualandris-Parisot L, Foulquier F, Grinfield S, Kan P, Duprat AM. Differentiation in microgravity of neural and muscle cells of a vertebrate (Amphibian). Adv Space Res 1998;22:303-8.  Back to cited text no. 58
    
59.
Demêmes D, Dechesne CJ, Venteo S, Gaven F, Raymond J. Development of the rat efferent vestibular system on the ground and in microgravity. Brain Res Dev Brain Res 2001;128:35-44.  Back to cited text no. 59
    
60.
Frigeri A, Iacobas DA, Iacobas S, Nicchia GP, Desaphy JF, Camerino DC, et al. Effect of microgravity on gene expression in mouse brain. Exp Brain Res 2008;191:289-300.  Back to cited text no. 60
    
61.
Inglis FM, Zuckerman KE, Kalb RG. Experience-dependent development of spinal motor neurons. Neuron 2000;26:299-305.  Back to cited text no. 61
    
62.
Ranjan A, Behari J, Mallick BN. Cytomorphometric changes in hippocampal CA1 neurons exposed to simulated microgravity using rats as model. Front Neurol 2014;5:1-10.  Back to cited text no. 62
    
63.
Monticone M, Liu Y, Pujic N, Cancedda R. Activation of nervous system development genes in bone marrow derived mesenchymal stem cells following spaceflight exposure. J Cell Biochem 2010;111:442-52.  Back to cited text no. 63
    
64.
Chen J, Liu R, Yang Y, Li j, Zhang X, Wang Z, et al. The simulated microgravity enhances the differentiation of mesenchymal stem cells into neurons. Neurosci Lett 2011;505:171-5.  Back to cited text no. 64
    
65.
Wang N, Wang H, Chen J, Zhang X, Xie J, Li Z, et al. The simulated microgravity enhances multipotential differentiation capacity of bone marrow mesenchymal stem cells. Cytotechnology 2014;66:119-31.  Back to cited text no. 65
    
66.
Zwart SR, Gregory JF, Zeisel SH, Gibson CR, Mader TH, Kinchen JM, et al. Genotype, B-vitamin status, and androgens affect spaceflight-induced ophthalmic changes. FASEB J 2016; 30:141-8.  Back to cited text no. 66
    
67.
Mader TH, Gibson CR, Lee AG. Choroidal folds in astronauts. Invest Ophthalmol Vis Sci 2016;57:592.  Back to cited text no. 67
    
68.
Corydon TJ, Mann V, Slumstrup L, Kopp S, Sahana J, Askou AL, et al. Reduced expression of cytoskeletal and extracellular matrix genes in human adult retinal pigment epithelium cells exposed to simulated microgravity. Cell Physiol Biochem 2016;40:1-17.  Back to cited text no. 68
    
69.
Simon SA, Advani S, McIntosh TJ. Temperature dependence of the repulsive pressure between phosphatidylcholine bilayers. Biophys J 1995;69:1473-83.  Back to cited text no. 69
    
70.
Gullingsrud J, Schulten K. Lipid bilayer pressure profiles and mechanosensitive channel gating. Biophys J 2004;86:3496-509.  Back to cited text no. 70
    
71.
Gong K, Feng SS, Go ML, Soew PH. Effects of pH on the stability and compressibility of DPPC/cholesterol monolayers at the air-water interface. Colloids Surf 2002;207:113-25.  Back to cited text no. 71
    
72.
Ermakov YA, Kamaraju K, Sengupta K, Sukharev S. Gadolinium ions block mechanosensitive channels by altering the packing and lateral pressure of anionic lipids. Biophys J 2010;98:1018-27.  Back to cited text no. 72
    
73.
Sieber M, Hanke W, Kohn FPM. Modification of membrane fluidity by gravity. Open J Biophys 2014;4:7.  Back to cited text no. 73
    
74.
Häder DP, Hemmersbach R, Lebert M. Gravity and the Behavior of Unicellular Organisms. Cambridge: Cambridge University Press; 2005 DOI: 10.1017/CBO9780511546211. [Last accessed on 2019 May 02].  Back to cited text no. 74
    
75.
Hauschild S, Tauber S, Lauber B, Thiel CS, Layer LE, Ullrich O. T cell regulation in microgravity - The current knowledge from in vitro experiments conducted in space, parabolic flights and ground-based facilities. Acta Astronautica 2014;104:365-77.  Back to cited text no. 75
    
76.
Wiedemann M, Kohn FPM, Roesner H, Hanke W. Self-organization and Pattern-formation in Neuronal Systems Under Conditions of Variable Gravity. Springer Publishing 2011. Available from: https://link.springer.com/book/10.1007/978-3-642-14472-1. [Last accessed on 2019 May 02].  Back to cited text no. 76
    
77.
Lee AG. How lipids affect the activities of integral membrane proteins. Biochimica et Biophysica Acta 2004;1666:62-87.  Back to cited text no. 77
    
78.
Heimburg T. Thermal Biophysics of Membranes. Weinheim, Germany: Wiley-VCH Verlag GmbH and Co. KGaA 2007. Available from: https://www.wiley.com/en-ae/Thermal+Biophysics+of+Membranes-p-9783527404711. [Last accessed on 2019 May 02].  Back to cited text no. 78
    
79.
Zanello LP, Aztiria E, Antollini S, Barrantes FJ. Nicotinic acetylcholine receptor channels are influenced by the physical state of their membrane environment. Biophys J 1996;70:2155-2164  Back to cited text no. 79
    
80.
Sieber M, Hanke W, Kohn FPM. Modification of membrane fluidity by gravity. Open J Biophys 2014;4:105-111.  Back to cited text no. 80
    
81.
Singla V, Reiter JF. The primary cilium as the cell's antenna: Signaling at a sensory organelle. Science 2006;313:629-33.  Back to cited text no. 81
    
82.
Satir P, Pedersen LB, Christensen ST. The primary cilium at a glance. J Cell Sci 2010;123:499-503.  Back to cited text no. 82
    
83.
Koch C, Segev I. The role of single neurons in information processing. Nat Neurosci. 2000;3:1171-7.  Back to cited text no. 83
    
84.
Cai X, Liang CW, Muralidharan S, Muralidharan S, Kao JP, Tang CM, Thompson SM. Unique roles of SK and Kv4.2 potassium channels in dendritic integration. Neuron 2004; 44:351-64.  Back to cited text no. 84
    
85.
Goldberg EM, Clark BD, Zagha E, Nahmani M, Erisir A, Rudy B. K+ channels at the axon initial segment dampen near-threshold excitability of neocortical fast-spiking GABAergic interneurons. Neuron 2008;58:387-400.  Back to cited text no. 85
    
86.
Sjöström PJ, Nelson SB. Spike timing, calcium signals and synaptic plasticity. Curr Opin Neurobiol 2002;12:305-14.  Back to cited text no. 86
    
87.
Shah MM, Hammond RS, Hoffman DA. Dendritic ion channel trafficking and plasticity. Trends Neurosci 2010;33:307-16.  Back to cited text no. 87
    
88.
Debanne D, Daoudal G, Sourdet V, Russier M. Brain plasticity and ion channels. J Physiol-Paris 2003;97:403-14.  Back to cited text no. 88
    
89.
Arnadottir J, Chalfie M. Eukaryotic mechanosensitive channels. Annu Rev Biophys 2010;39:111-37.  Back to cited text no. 89
    
90.
Goldermann M, Hanke W. Ion channel are sensitive to gravity changes. Microgravity Sci Technol 2001;13:35-38.  Back to cited text no. 90
    
91.
Klinke N, Goldermann M, Hanke W. The properties of alamethicin incorporated into planar lipid bilayers under the influence of microgravity. Acta Astronautica 2000;47:771-3.  Back to cited text no. 91
    
92.
Wiedemann M, Rahmann H, Hanke W. Gravitational impact on ion channels incorporated into planar lipid bilayers. In: TiTien and Ottova, editors. Planar lipid bilayers and their applications. Elsevier Sciences 1993. Available from: https://www.elsevier.com/books/planar-lipid-bilayers/sattelle/978-0-12-322995-3. [Last accessed on 2019 May 02].  Back to cited text no. 92
    
93.
Richard S, Henggeler D, Ille F, Beck SV, MoeckliIan M, Ian Forster C, et al. A semi-automated electrophysiology system for recording from Xenopus oocytes under microgravity conditions. Microgravity Sci Technol 2012;24:237-44.  Back to cited text no. 93
    
94.
Schaffhauser DF, Andrini O, Ghezzi C, Forster IC, Obregon AF, Egli M, et al. Microfluidic platform for electrophysiological studies on Xenopus laevisoocytes under varying gravity levels. Lab chip 2011;11:3471-3478.  Back to cited text no. 94
    
95.
Hanke W, Fernandes de Lima V, Wiedemann M, Meissner K. Microgravity dependence of excitable biological and physicochemical media. Protoplasma 2006;229:235.  Back to cited text no. 95
    
96.
Crestini A, Zona C, Sebastiani P, Pieri M, Caracciolo V, Malvezzi-Campeggi L, et al. Effects of simulated microgravity on the development and maturation of dissociated cortical neurons. In Vitro Cell Dev Biol Anim 2004;40:159-65.  Back to cited text no. 96
    
97.
Ranjan A, Behari J, Mallick BN. Cytomorphometric changes in hippocampal CA1 Neurons exposed to simulated microgravity using rats as model. Front Neurol 2014;5:77.  Back to cited text no. 97
    
98.
Meissner K, Hanke W. Action potential properties are gravity dependent. Microgravity Science and Technology 2005;17:38-43. Available from: http://adsabs.harvard.edu/abs/2005MicST.17.38M.  Back to cited text no. 98
    
99.
Kohn FPM, Ritzmann R. Gravity and neuronal adaptation, in vitro and in vivo-from neuronal cells up to neuromuscular responses: A first model. EurBiophys J 2017;47:97-107.  Back to cited text no. 99
    
100.
Spudis PD. An argument for human exploration of the moon and Mars. Am Sci 1992;80:269-77.  Back to cited text no. 100
    
101.
Hilbig R, Gollhofer A, Bock O, Manzey D. Sensory Motor and Behavioral Research in Space. Cham: Springer International Publishing; 2017. Available from: https://www.springer.com/us/book/9783319682006. [Last accessed on 2019 May 02].  Back to cited text no. 101
    


    Figures

  [Figure 1], [Figure 2]



 

Top
Print this article  Email this article
   
Online since 20th March '04
Published by Wolters Kluwer - Medknow