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Prolonged residence of mice in spaceflight is a scientifically robust and ethically ratified model of muscle atrophy caused by continued unloading. Under the Rodent Research Program of the National Aeronautics and Space Administration (NASA), we assayed the large‐scale mRNA and metabolomic perturbations in the quadriceps of C57BL/6j male mice that lived in spaceflight (FLT) or on the ground (control or CTR) for approximately 4 weeks. The wet weights of the quadriceps were significantly reduced in FLT mice. Next‐generation sequencing and untargeted mass spectroscopic assays interrogated the gene‐metabolite landscape of the quadriceps. A majority of top‐ranked differentially suppressed genes in FLT encoded proteins from the myosin or troponin families, suggesting sarcomere alterations in space. Significantly enriched gene‐metabolite networks were found linked to sarcomeric integrity, immune fitness, and oxidative stress response; all inhibited in space as per in silico prediction. A significant loss of mitochondrial DNA copy numbers in FLT mice underlined the energy deprivation associated with spaceflight‐induced stress. This hypothesis was reinforced by the transcriptomic sequencing–metabolomics integrative analysis that showed inhibited networks related to protein, lipid, and carbohydrate metabolism, and adenosine triphosphate (ATP) synthesis and hydrolysis. Finally, we discovered important upstream regulators, which could be targeted for next‐generation therapeutic intervention for chronic disuse of the musculoskeletal system. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.

Post-traumatic stress disorder (PTSD) is an anxiety disorder that can arise due to exposure to a potentially traumatic event (PTE). Using "cage-within-cage resident-intruder" protocol, subject C57BL/6J mice were exposed to aggressor mice for 10 days with 24 hours rest prior to harvesting. The symbiotic influence of microbiota on the nervous system and behavior has been receiving profound interest. In this longitudinal study, we are focusing on the effect of social stress on the microbiome by sequencing for 16S ribosomal RNA (16S rRNA) amplicon on the Illumina MiSeq platform. Fecal samples were collected at 2 day intervals during the 10 day protocol from control as well as subject mice. DNA was isolated using a kit from MO BIO followed by amplification of variable V3 and V4 region of the 16S rRNA amplicon using the Illumina 16S Metagenomics Library Preparation Protocol. The samples were barcoded using Nextera index primers and pooled in preparation for MiSeq sequencing. We will be able to characterize the ...

The gastrointestinal tract is colonized by an enormous array of microbial symbiotes and pathogens. The symbiote influence of gut microbiota on the nervous system and behavior has been receiving profound interest. Rodent studies have provided suggestive evidence that probiotics (e.g. Lactobacillus and Bifidobacterium) can influence behavior. Using "cage-within-cage resident-intruder" model, subject C57BL/6J mice were exposed to aggressors for 6 h daily for 5 or 10 days. After one day of recovery inflammatory cardiac histopathologies were prevalent. Here we report metagenomics and metabolomics approaches to understanding the microbiome activity in our social stress model of mice. Plasma samples were compared between aggressor-exposed and control mice using various Mass Spec-based techniques. Large effects of microbiome composition on plasma biochemistry were observed, and several microbiome-affected molecules such as hippurate, phenylpropionylglycine, and 3-phenylpropionic were identified in plasma. We also...