Mechanisms Underlying Neuroplasticity in the Nucleus Tractus Solitarii Following Hindlimb Unloading in Rats

The roles of gravitational load or anti-gravitational muscular activities on the growth and development of motor function and/or anti-gravity muscle, soleus, had been investigated. In this review, the responses of growth-associated changes in swimming [1, 2] and/or surface righting performance [3], spatial learning and memory functions [4], and hippocampal neurogenesis [5] or protein expression [6] to hindlimb unloading (HU) by hindlimb suspension or spaceflight during neonatal growing period in rats were discussed. Effects on the morphological and contractile properties, distribution of neuromuscular junction in single muscle fibers, sampled from tendon-to-tendon, and roles of satellite cells and myonuclei in the regulation of these properties [7–9] were also reviewed.

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Inhibition of Histone Deacetylases 4 and 5 Reduces Titin Proteolysis and Prevents Reduction of TTN Gene Expression in Atrophied Rat Soleus Muscle after Seven-Day Hindlimb Unloading

Doklady Biochemistry and Biophysics ◽

10.1134/s1607672920060058 ◽

2020 ◽

Vol 495 (1) ◽

pp. 338-341

Author(s):

Yu. V. Gritsyna ◽

A. D. Ulanova ◽

S. S. Popova ◽

A. G. Bobylev ◽

V. K. Zhalimov ◽

...

Keyword(s):

Gene Expression ◽

Soleus Muscle ◽

Histone Deacetylases ◽

Hindlimb Unloading ◽

Rat Soleus Muscle

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Placenta-Expanded Stromal Cell Therapy in a Rodent Model of Simulated Weightlessness

Cells ◽

10.3390/cells10040940 ◽

2021 ◽

Vol 10 (4) ◽

pp. 940

Author(s):

Linda Rubinstein ◽

Amber M. Paul ◽

Charles Houseman ◽

Metadel Abegaz ◽

Steffy Tabares Ruiz ◽

...

Keyword(s):

Health Risks ◽

Stromal Cells ◽

Therapeutic Potential ◽

Medical Intervention ◽

Hindlimb Unloading ◽

Simulated Weightlessness ◽

Potential Health ◽

Long Duration ◽

Induced Changes ◽

Splenic Atrophy

Long duration spaceflight poses potential health risks to astronauts during flight and re-adaptation after return to Earth. There is an emerging need for NASA to provide successful and reliable therapeutics for long duration missions when capability for medical intervention will be limited. Clinically relevant, human placenta-derived therapeutic stromal cells (PLX-PAD) are a promising therapeutic alternative. We found that treatment of adult female mice with PLX-PAD near the onset of simulated weightlessness by hindlimb unloading (HU, 30 d) was well-tolerated and partially mitigated decrements caused by HU. Specifically, PLX-PAD treatment rescued HU-induced thymic atrophy, and mitigated HU-induced changes in percentages of circulating neutrophils, but did not rescue changes in the percentages of lymphocytes, monocytes, natural killer (NK) cells, T-cells and splenic atrophy. Further, PLX-PAD partially mitigated HU effects on the expression of select cytokines in the hippocampus. In contrast, PLX-PAD failed to protect bone and muscle from HU-induced effects, suggesting that the mechanisms which regulate the structure of these mechanosensitive tissues in response to disuse are discrete from those that regulate the immune- and central nervous system (CNS). These findings support the therapeutic potential of placenta-derived stromal cells for select physiological deficits during simulated spaceflight. Multiple countermeasures are likely needed for comprehensive protection from the deleterious effects of prolonged spaceflight.

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Immunological and hematological outcomes following protracted low dose/low dose rate ionizing radiation and simulated microgravity

Scientific Reports ◽

10.1038/s41598-021-90439-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Amber M. Paul ◽

Eliah G. Overbey ◽

Willian A. da Silveira ◽

Nathaniel Szewczyk ◽

Nina C. Nishiyama ◽

...

Keyword(s):

Low Dose ◽

Transforming Growth Factor ◽

Expression Profiles ◽

Transforming Growth Factor Β ◽

Hindlimb Unloading ◽

B Cell Differentiation ◽

Specific Regulation ◽

Β Receptor ◽

Gene Orthologs ◽

Whole Transcriptome

AbstractUsing a ground-based model to simulate spaceflight [21-days of single-housed, hindlimb unloading (HLU) combined with continuous low-dose gamma irradiation (LDR, total dose of 0.04 Gy)], an in-depth survey of the immune and hematological systems of mice at 7-days post-exposure was performed. Collected blood was profiled with a hematology analyzer and spleens were analyzed by whole transcriptome shotgun sequencing (RNA-sequencing). The results revealed negligible differences in immune differentials. However, hematological system analyses of whole blood indicated large disparities in red blood cell differentials and morphology, suggestive of anemia. Murine Reactome networks indicated majority of spleen cells displayed differentially expressed genes (DEG) involved in signal transduction, metabolism, cell cycle, chromatin organization, and DNA repair. Although immune differentials were not changed, DEG analysis of the spleen revealed expression profiles associated with inflammation and dysregulated immune function persist to 1-week post-simulated spaceflight. Additionally, specific regulation pathways associated with human blood disease gene orthologs, such as blood pressure regulation, transforming growth factor-β receptor signaling, and B cell differentiation were noted. Collectively, this study revealed differential immune and hematological outcomes 1-week post-simulated spaceflight conditions, suggesting recovery from spaceflight is an unremitting process.

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