Secretory proteins produced by salivary glands are stored in granules and released into saliva. Rodent salivary glands are a reliable experimental model because they are morphologically and functionally similar to those of humans. To determine if the effects of microgravity on secretory proteins are increased on extended flights, their expression in mouse parotid glands, morphological, immuno- cytochemical, and biochemical/molecular methods were employed. Acinar cells of STS-135 (13 day) and Bion-M1 (30 day) flight animals showed an increase of autophagy and apoptosis, while duct cells contained vacuoles with endocytosed proteins. In STS-135, decreases were seen in the regulatory subunit of type II protein kinase A (RII) by Western blotting, and demilune cell and parotid protein (DCPP) and α- amylase (p<0.01) by immunogold labeling, while proline-rich proteins (PRPs, p<0.001) and parotid secretory protein (PSP, p<0.05) were increased. These results suggest microgravity effects on secretion are function-dependent. Microarray analyses showed significant changes in the expression of a number of genes, including components of the cyclic-3',5',-adenosine monophosphate (cyclic AMP) signaling pathway. Compared to habitat ground controls, mice from both flights exhibited altered expression of cyclic AMP-specific phosphodiesterases, adenylate cyclase isoforms, and several A-kinase anchoring proteins. Bion-M1 flight mice showed increases in gene expression for lysozyme and amylase, a decrease in PRPs, and RII expression was unchanged from control values. Secretory protein expression is altered by travel in space, representing a reversible adjustment to microgravity conditions. Ultimately, the goal is to develop a test kit using saliva — an easily obtained body fluid — to assess the physiologic effects of travel in space.
Related URLs:
http://gravitationalandspacebiology.org/index.php/journal/article/viewFile/678/697
Research Containing: animal enclosure module
Evaluation of rodent spaceflight in the NASA animal enclosure module for an extended operational period (up to 35 days)
The National Aeronautics and Space Administration Animal Enclosure Module (AEM) was developed as a self-contained rodent habitat for shuttle flight missions that provides inhabitants with living space, food, water, ventilation, and lighting, and this study reports whether, after minimal hardware modification, the AEM could support an extended term up to 35 days for Sprague-Dawley rats and C57BL/6 female mice for use on the International Space Station. Success was evaluated based on comparison of AEM housed animals to that of vivarium housed and to normal biological ranges through various measures of animal health and well-being, including animal health evaluations, animal growth and body masses, organ masses, rodent food bar consumption, water consumption, and analysis of blood contents. The results of this study confirmed that the AEMs could support 12 adult female C57BL/6 mice for up to 35 days with self-contained RFB and water, and the AEMs could also support 5 adult male Sprague-Dawley rats for 35 days with external replenishment of diet and water. This study has demonstrated the capability and flexibility of the AEM to operate for up to 35 days with minor hardware modification. Therefore, with modifications, it is possible to utilize this hardware on the International Space Station or other operational platforms to extend the space life science research use;of mice and rats.
Related URLs:
http://www.nature.com/articles/npjmgrav20162
Ground-based assessment of JAXA mouse habitat cage unit by mouse phenotypic studies
The Japan Aerospace Exploration Agency developed the mouse Habitat Cage Unit (HCU) for installation in the Cell Biology Experiment Facility (CBEF) onboard the Japanese Experimental Module (“Kibo”) on the International Space Station. The CBEF provides “space-based controls” by generating artificial gravity in the HCU through a centrifuge, enabling a comparison of the biological consequences of microgravity and artificial gravity of 1 g on mice housed in space. Therefore, prior to the space experiment, a ground-based study to validate the habitability of the HCU is necessary to conduct space experiments using the HCU in the CBEF. Here, we investigated the ground-based effect of a 32-day housing period in the HCU breadboard model on male mice in comparison with the control cage mice. Morphology of skeletal muscle, the thymus, heart, and kidney, and the sperm function showed no critical abnormalities between the control mice and HCU mice. Slight but significant changes caused by the HCU itself were observed, including decreased body weight, increased weights of the thymus and gastrocnemius, reduced thickness of cortical bone of the femur, and several gene expressions from 11 tissues. Results suggest that the HCU provides acceptable conditions for mouse phenotypic analysis using CBEF in space, as long as its characteristic features are considered. Thus, the HCU is a feasible device for future space experiments.
Related URLs:
http://www.ncbi.nlm.nih.gov/pubmed/26822934
Genetic and Apoptotic Changes in Lungs of Mice Flown on the STS-135 Mission in Space.
AIM: The goal of the study was to evaluate changes in lung status due to spaceflight stressors that include radiation above levels found on Earth.;MATERIALS AND METHODS: Within hours after return from a 13-day mission in space onboard the Space Shuttle Atlantis, C57BL/6 mice (FLT group) were euthanized; mice housed on the ground in similar animal enclosure modules served as controls (AEM group). Lung tissue was collected to evaluate the expression of genes related to extracellular matrix (ECM)/adhesion and stem cell signaling. Pathway analysis was also performed. In addition, immunohistochemistry for stem cell antigen-1 (SCA-1), the terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay for apoptosis, and staining for histological characteristics were performed.;RESULTS: There were 18/168 genes significantly modulated in lungs from the FLT group (p<0.05 vs. AEM); 17 of these were up-regulated and one was down-regulated. The greatest effect, namely a 5.14-fold increase, was observed on Spock1 (also known as Spark/osteonectin), encoding a multi-functional protein that has anti-adhesive effects, inhibits cell proliferation and regulates activity of certain growth factors. Additional genes with increased expression were cadherin 3 (Cdh3), collagen, type V, alpha 1 (Col5a1), integrin alpha 5 (Itga5), laminin, gamma 1 (Lamc1), matrix metallopeptidase 14 (Mmp14), neural cell adhesion molecule 1 (Ncam1), transforming growth factor, beta induced (Tgfbi), thrombospondin 1 (Thbs1), Thbs2, versican (Vcan), fibroblast growth factor receptor 1 (Fgfr1), frizzled homolog 6 (Fzd6), nicastrin (Ncstn), nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 4 (Nfatc4), notch gene homolog 4 (Notch4) and vang-like 2 (Vangl2). The down-regulated gene was Mmp13. Staining for SCA-1 protein showed strong signal intensity in bronchiolar epithelial cells of FLT mice (p<0.05 vs. AEM). TUNEL positivity was also significantly higher in the FLT mice (p<0.05 vs. AEM), but no consistent histological differences were noted. CONCLUSION: The results demonstrate that spaceflight-related stress had a significant impact on lung integrity, indicative of tissue injury and remodeling.
Related URLs:
http://www.ncbi.nlm.nih.gov/pubmed/26130787