Signs of Müller cell gliotic response found in the retina of newts exposed to real and simulated microgravity

Grigoryan, E. N.; Anton, Hermann Josef; Poplinskaya, V. A.; Aleinikova, K. S.; Domaratskaya, E. I.; Novikova, Yu. P.; Almeida, Eduardo

doi:10.1016/j.asr.2012.02.025

Cited by 7 publications

(14 citation statements)

References 21 publications

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“…It is noteworthy that in the newt retina, which is known for its unique restorative capacity, Müller cells also respond to damage by proliferation and formation of increasingly dense and thick accessory prolongations. This has been observed in the experiments described above as well as under conditions of retinal detachment and other retinal injuries [29].…”

Section: Discussionsupporting

confidence: 64%

Retinal remodeling under conditions of organotypic 3D culturing in vitro and after damage in vivo in lower and higher vertebrates

Grigoryan¹,

Poplinskaya²,

Novikova³

2016

New Front Ophthalmol

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Comparative analysis of retinal remodeling (RR) after damage in species capable and incapable to mobilize endogenous cell reserves provides an insight as to how limitations on retina restoration in humans can be overcome. RR is a phenomenon accompanying the loss of photoreceptor cells in various diseases and experimental models. Our study on the adult newt and rat retinas damaged in vivo or cultured in vitro is an attempt to reveal universal and specific features of RR in the aspects of cell behavior and tissue anatomy. When newt retina is damaged by light in vivo or placed in tissue culture, a regenerative response is observed from four cell populations: retinal pigment epithelium (RPE), retinal growth zone, displaced bipolar-like cells, and macroglia. Cells of the first three populations migrate, divide, and differentiate to replace lost photoreceptors, while the macroglia shows a gliotic response. In the rat retina, RPE cells in damaged sites change their phenotype, migrate, rarely divide, and often undergo apoptosis; in parallel, interneurons move to the site of photoreceptor damage, and Muller cells respond by hypertrophy. Cells at the periphery of the rat retina are not involved in RR, and there are no signs of cell division and reprogramming for the functional replacement of lost neurons. Thus, RR events in the rat and newt are comparable, except that cell behavior during RR in the newt follows the developmental pattern and, hence, this process can be regarded as true retinal regeneration rather than mere retinal reconstruction, as in the rat.

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Section: Discussionsupporting

confidence: 64%

Retinal remodeling under conditions of organotypic 3D culturing in vitro and after damage in vivo in lower and higher vertebrates

Grigoryan¹,

Poplinskaya²,

Novikova³

2016

New Front Ophthalmol

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“…MG stem-like cells of newt and rat retina can divide in roller 3D culture in the absence of mitogenic factors in the media [95,96]. Our experiments showed that MG cells of newt in vivo are also sensitive to real and simulated microgravity [97].…”

Section: Müller Gliamentioning

confidence: 59%

“…Microsurgical retinal detachment in newts caused growth of the MG population (assessed by the number of [ 3 H]-TdRlabeled MG cells and the number of their accessory prolongations), which was further increased by simulated microgravity, reaching a 1.5-2.0-fold difference with 1 g control after 7 days in clinostat [79,97]. Real microgravity onboard Bion 11 biosatellite also promoted MG amplification (40% increase in a number of cells expressing its marker protein, Gfap) in newts regenerating retina 4 weeks after optic nerve crosscut [97,98]. Lensectomy led to increased immunostaining for both Gfap and stress protein Hsp90, which was more prominent in microgravity during Foton M3 spaceflight than in 1 g controls ( Fig.…”

Section: Müller Gliamentioning

confidence: 99%

“…Lensectomy led to increased immunostaining for both Gfap and stress protein Hsp90, which was more prominent in microgravity during Foton M3 spaceflight than in 1 g controls ( Fig. 5) [66,97]. In cases where retina is not directly disturbed, MG cells may respond to changes in intraocular pressure (for example, its drop after lensectomy); laser-induced increase in intraocular pressure increases expression of GFAP in MG cells of rat retina in vivo [99].…”

Section: Müller Gliamentioning

confidence: 99%

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Behavior of Stem-Like Cells, Precursors for Tissue Regeneration in Urodela, Under Conditions of Microgravity

Grigoryan

Radugina

2019

Stem Cells and Development

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We summarize data from our experiments on stem-like cell-dependent regeneration in amphibians in microgravity. Considering its deleterious effect on many tissues, we asked whether microgravity is compatible with reparative processes, specifically activation and proliferation of source cells. Experiments were conducted using tailed amphibians, which combine profound regenerative capabilities with high robustness, allowing an in vivo study of lens, retina, limb, and tail regeneration in challenging settings of spaceflight. Microgravity promoted stem-like cell proliferation to a varying extent (up to 2-fold), and it seemed to speed up source cell dedifferentiation, as well as sequential differentiation in retina, lens, and limb, leading to formation of bigger and more developed regenerates than in 1g controls. It also promoted proliferation and hypertrophy of Müller glial cells, eliciting a response similar to reactive gliosis. A significant increase in stem-like cell proliferation was mostly beneficial for regeneration and only in rare cases caused moderate tissue growth abnormalities. It is important that microgravity yielded a lasting effect even if applied before operations. We hypothesize on the potential mechanisms of gravity-dependent changes in stem-like cell behavior, including fibroblast growth factor 2 signaling pathway and heat shock proteins, which were affected in our experimental settings. Taken together, our data indicate that microgravity does not disturb the natural regenerative potential of newt stem-like cells, and, depending on the system, even stimulates their dedifferentiation, proliferation, and differentiation. We discuss these data along with publications on mammalian stem cell behavior in vitro and invertebrate regeneration in vivo in microgravity. In vivo data are very scarce and require further research using contemporary methods of cell behavior analysis to elucidate mechanisms of stem cell response to altered gravity. They are relevant for both practical applications, such as managing human reparative responses in spaceflight, and fundamental understanding of stem cell biology.

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“…After 14 days of microgravity exposure, the expression of astrocyte-specific GFAP was observed to decrease significantly (Day et al, 1998 ); however, the same effect was not observed with long-term microgravity exposure (Bellone et al, 2016 ). In an animal study (Grigoryan et al, 2012 ), GFAP levels increased during exposure to long-term microgravity. Mao et al reported an increase in perivascular reactive GFAP astrocytes in the hippocampus of mice who had spent 35 days on the International Space Station when compared to control mice on the ground (Mao et al, 2020 ).…”

Section: Discussionmentioning

confidence: 97%

Elevated biomarkers of neural injury in older adults following head-down bed rest: links to cardio-postural deconditioning with spaceflight and aging

Blaber,

Sadeghian,

Naz Divsalar

et al. 2023

Front. Hum. Neurosci.

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IntroductionProlonged physical inactivity with bed rest or spaceflight is associated with cardiovascular and neuromuscular deconditioning; however, its impact on neural integrity of cardio-postural reflexes and possible mitigation with exercise has not been examined. We assessed the association between the physiological deconditioning of bed rest immobilization with neural injury markers and the effects of 60–75 min of daily exercise.MethodsData were collected as part of a randomized clinical trial (clinicaltrials.gov identifier: NCT04964999) at the McGill University Medical Centre. Twenty-two 55- to 65-year-old healthy volunteers gave informed consent and took part. Within sex, participants were randomly assigned to exercise (60- to 75-min daily) or control (inactive) groups and spent 14 days in continuous 6° head-down tilt. Neural injury [neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), total tau (t-Tau), myelin basic protein (MBP), brain-derived neurotrophic factor (BDNF), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1)], as well as interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and insulin-like growth factor 1 (IGF-1) biomarkers were measured before, during, and after bed rest. The false discovery rate with Huber M-estimation was used to correlate changes in biomarkers with cardiovascular and muscular function changes over bed rest.ResultsBed rest elevated NfL, GFAP, TNF-α, and IL-6 in all participants and reduced IGF-1 in females only. With standing, changes in heart rate, blood pressure, and lower limb muscle motoneuron activity correlated with changes in TNF-α and BDNF. Baroreflex control, leg muscle maximal voluntary contraction, and postural sway are correlated with GFAP and NfL. Exercise participants had fewer interactions than control participants, but significant correlations still existed, with both groups exhibiting similar reductions in orthostatic tolerance.DiscussionAn hour of daily exercise in older persons otherwise immobilized for 2 weeks did not abate bed rest-induced increases in serum signatures of neural injury or pro-inflammatory markers. Exercise reduced the number of physiological interactions of biomarkers, but significant cardio-postural correlations remained with no protection against post-bed rest orthostatic intolerance. The identification of associations of inflammatory and neural injury biomarkers with changes in cardio-postural physiology and exercise points to biotherapeutic opportunities and improved exercise interventions for astronauts and individuals in bed rest.Clinical trial registrationhttps://www.clinicaltrials.gov/search?cond=NCT04964999, identifier: NCT04964999.

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Signs of Müller cell gliotic response found in the retina of newts exposed to real and simulated microgravity

Cited by 7 publications

References 21 publications

Retinal remodeling under conditions of organotypic 3D culturing in vitro and after damage in vivo in lower and higher vertebrates

Retinal remodeling under conditions of organotypic 3D culturing in vitro and after damage in vivo in lower and higher vertebrates

Behavior of Stem-Like Cells, Precursors for Tissue Regeneration in Urodela, Under Conditions of Microgravity

Elevated biomarkers of neural injury in older adults following head-down bed rest: links to cardio-postural deconditioning with spaceflight and aging

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